1 s2.0 S1773224723005725 Main

Journal of Drug Delivery Science and Technology 86 (2023) 104720
Contents lists available at ScienceDirect
Journal of Drug Delivery Science and Technology

journal homepage: www.elsevier.com/locate/jddst
Review article
Sunscreens: A comprehensive review with the application

of nanotechnology
Vivek P. Chavda a, *, Devarshi Acharya b, 1, Vivek Hala b, 1, Shilpa Daware d, Lalitkumar
K. Vora c, **
a
Department of Pharmaceutics and Pharmaceutical Technology, LM College of Pharmacy, Ahmedabad, 380009, India
b
Pharmacy Section, LM College of Pharmacy, Ahmedabad, 380009, India
c
School of Pharmacy, Queen’s University Belfast, 97 Lisburn Road, BT9 7BL, UK
d
Department of Pharmaceutics, School of Pharmacy, Vishwakarma University, Survey No 2,3,4 Laxminagar, Kondhwa (Bk.), Pune, Maharashtra, India
A R T I C L E I N F O A B S T R A C T
Keywords: Ultraviolet (UV) radiation is the primary cause of various skin diseases, necessitating the need for UV protection.
Sunscreens Topical sunscreens are the most commonly used method to achieve this. However, traditional sunscreen for
Nanoparticles mulations have limitations that hinder their widespread use. Nanotechnology has played a significant role in the
UV radiation
development of new sunscreen formulations that aim to address the limitations of traditional sunscreens. These
Sun protection factor (SPF)
Cosmeceuticals
advancements have brought about several improvements in terms of UV protection and cosmetic appeal. The
review explores different nanosystems utilized in sunscreen formulations, including polymeric nanoparticles,
liposomes, nanostructure lipid carriers, solid lipid nanoparticles, nanoemulsions, hydrogels, nanocrystals, mes
oporous silica particles, niosomes, ethosomes, transfersomes, transethosomes, and sunspheres. These nano
systems enhance the safety and effectiveness of sunscreens, improving their distribution, photostability, SPF,
UVA protection, and water resistance. Combinational sunscreens, which combine multiple active ingredients, are
also discussed. They offer broad-spectrum protection against UVA and UVB radiation, providing comprehensive
sun protection. The article reviews evaluation methods for sunscreens, such as SPF, UVA protection, and water
resistance. SPF measures the level of UVB protection, while UVA protection indicates defense against UVA ra
diation. Water resistance assesses the sunscreen’s durability after exposure to water or sweat. Additionally, the
article addresses the safety, regulation, and challenges associated with nanosystem-based sunscreens. Safety
considerations and regulatory frameworks ensure the products’ safety for human health and the environment.
Formulation stability, potential toxicity concerns, and lack of public awareness are also discussed as challenges.
In summary, nanotechnology-based sunscreens offer promising advancements in UV protection. The utilization
of various nanosystems improves safety and efficacy. Ongoing research and regulatory efforts are vital to ensure
the continued development and safe use of these nanosystems in sunscreens.
1. Introduction these, UV radiation is the most harmful, as it has the highest energy. The
UV rays are further divided into three subtypes: 1) ultraviolet A rays
The sun radiates various types of radiation, such as infrared (IR), (UVA), 2) ultraviolet B rays (UVB), and 3) ultraviolet C rays (UVC). The
visible light, and ultraviolet (UV) radiation [1]. All this radiation comes lowest energy and highest wavelength of all UV ray types are found in
under the electromagnetic spectrum, which ranges from 100 nm to 1 UVA, which has a wavelength of 320–400 nm and, due to its low energy,
mm. The IR rays have the highest wavelength (0.7 μm–1000 μm) [2], causes the least damage. UVB, which has an intermediate wavelength of
followed by visible light in the range of 380–700 nm [3], and ultraviolet 290–320 nm, is next, and UVC, which has the highest energy and lowest
(UV) rays contain the shortest wavelength of 10–400 nm [4]. From wavelength, is last (100–280 nm) and has the most potential to cause
* Corresponding author. Department of Pharmaceutics and Pharmaceutical Technology, L.M. College of Pharmacy, Navrangpura, Ahmedabad, Gujarat, India.
** Corresponding author. School of Pharmacy, Queen’s University Belfast, 97 Lisburn Road, BT9 7BL, UK.
E-mail addresses: [email protected] (V.P. Chavda), [email protected] (L.K. Vora).
1
Contributed equally.
https://doi.org/10.1016/j.jddst.2023.104720
Received 24 April 2023; Received in revised form 12 June 2023; Accepted 29 June 2023
Available online 30 June 2023
1773-2247/© 2023 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
V.P. Chavda et al. Journal of Drug Delivery Science and Technology 86 (2023) 104720
damage (Fig. 1 shows the type of UV radiation, their permeation in the (BCC) and squamous cell carcinomas (SCC). Apart from UV, IR, and
skin and related diseases) [5]. visible light also negatively affect the skin. It causes modifications of the
The ozone layer present in the Earth’s atmosphere is able to absorb stratum corneum and degradation of the dermal matrix [12]. From the
UVC completely, while UVB is partially absorbed. Hence, the majority of above-mentioned facts, it is clear that sun rays have many harmful ef
UV rays coming to the earth are UVA (~95%), and some portions are fects, but along with the harmful effects, sun rays have various advan
UVB (~5%). Both of these types of radiation have the ability to cause tages, such as improved cardiovascular health by assisting in the
DNA damage [6]. UVA mainly causes tanning and aging of the skin. UVB formation of nitric oxide that leads to vasodilation which ultimately
easily penetrates into the deeper layers of the skin, which ultimately reduces the blood pressure, antimicrobial activity, and the production of
causes various conditions, such as sunburn (reddening of the skin due to vitamin D [13–16].
the inflammatory response induced by UVB) [7]. UV radiation is also Sun damage can be prevented by taking proper measures. According
one of the radiations which are responsible for the generation of reactive to the World Health Organization (WHO), clothes, shades, sunglasses,
oxygen species (ROS) in the skin [8,9]. ROS have the ability to initiate and hats provide the best protection when they are used together with
photochemical reactions and skin photosensitization. Melanin, a natural sunscreen, which is spread on the exposed body parts [17]. When sun
antioxidant synthesized in the skin, prevents damage due to UV either by screens are used daily, they prevent skin cancer incidence and prema
neutralizing or/and scavenging the ROS or by absorbing and dissipating ture skin aging [18]. There are a variety of skin colors, and UV
the energy [10]. Additionally, long-term UV exposure gives rise to some sensitivity varies depending on the skin color. Resistance to sunburn and
serious complications, such as acute or chronic eye disorders and skin higher UV tolerance is seen in darker skin tones, but they are also sus
cancer [11]. Skin cancer is broadly divided into two types: 1) malignant ceptible to damage induced by UV radiation. Cancers cannot be diag
melanomas (highest mortality rate) and 2) nonmelanoma keratinocyte nosed at an early stage, as sunburn and skin tanning are not readily
cancers (most prevalent cancer), which include basal cell carcinomas observable in dark skin tones [19]. Hence, one should utilize sunscreens
Fig. 1. Types of UV radiation along with their penetration power into the skin and associated diseases.
2
on a day-to-day basis, regardless of skin type. Similarly, Health Canada (HC) has approved 22 ingredients. The Euro
pean Commission (EC) and Australian Therapeutic Goods Administra
2. Sunscreen UV-filters tion (TGA) have approved 29 and 31 ingredients, respectively [24,25].
Ultimately, the National Medical Products Administration (NMPA)
In simple terms, sunscreens can be defined as formulations that regulatory agency of China approved 27 active ingredients. The utili
protect the skin from damage by UV rays through an active ingredient zation of UV filters in sunscreen is enhanced due to the development of
with the ability to scatter, absorb, or reflect UV rays. sunscreens, at nanotechnology [26,27]. “An insoluble or biopersistent and intention
present, are mainstream for photoprotection. They contain either ally manufactured material with one or more external dimensions, or an
organic or inorganic UV filters that aid in their UV protection properties internal structure, on the scale from 1 to 100 nm” defines nanomaterials
(the classification of UV filters is given in Fig. 2). according to EC Regulation No 1223/2009. Over the last three decades,
inorganic filters such as ZnO and TiO2 have been widely used as active
ingredients. The reason for this is that they are approved in most
2.1. Organic or inorganic filters countries. In most regulatory frameworks, the particle size of these
inorganic filters is not mentioned. The only exception is EC, which has
The organic UV filter can further be classified by its ability to absorb been mentioned as nano TiO2 and nano ZnO in the subcategory of
specific types of UV radiation. If they can absorb UVA radiation then inorganic filters. The use of this nanoparticle-based sunscreen is still a
they are UVA filters and similarly, UVB-absorbing filters are known as question because of its safety issue. However, until now, no evidence has
UVB. Furthermore, some filters that can absorb both UVA and UVB are been found that can prove them toxic. Approved sunscreen UV filters
known as broad-spectrum UV filters. Currently, inorganic UV filter- through various regulatory agencies are mentioned in Table 1.
loaded sunscreens are extensively used because they do not penetrate
deeper into the skin, which reduces allergic reaction occurrence. The
major drawback is the whitish hue that is formed due to the scattering of 2.2. Nature derived UV-filters
light. However, this problem can be overcome by either utilizing
nanotechnology or by the addition of universal skin tone tints [20–22]. In sunscreen formulations, various natural molecules are being used
Different regulatory bodies around the world have approved due to their excellent effects on the skin with photoprotective effects
different compounds for their use as active ingredients. The United through various mechanisms. These biomacromolecules include carot
States Food and Drug Administration (U.S.FDA) regulatory agency of the enoids, phenolic compounds, vitamin C, vitamin E, and flavonoid
United States has approved 16 sunscreen active ingredients [23]. compounds. Carotenoids exert photoprotective action by absorbing UV
Fig. 2. The classification of various molecules used in the sunscreen formulation as UV filters.
3
Table 1
UV filters approved for sunscreen formulations.
Name of Ingredients Molecular Formula Other Name Effective Radiation Agencies that Maximum permitted
Range have Approved concentration (w/w)a
Avobenzone C20H22O3 Parsol 1789, Butyl UVA-I U.S.FDA, HC, 3% (U.S.FDA, HC), 5%
methoxydibenzoylmethane (BMDM) TGA, EU and (TGA, EU, and NMPA)
NMPA
Aminobenzoic acid C7H7NO2 Para-amino benzoic acid (PABA) UVB U.S.FDA, HC, 15%
TGA
3-Benzylidene camphor C17H20O 3BC UVB NMPA 2%
Bemotrizinol C38H49N3O5 Tinosorb S, Bemotrizinolum, Bis- UVA-I (partially), HC, TGA, EU, and 6% (HC), 10% (TGA,
ethylhexyloxyphenol methoxyphenyl UVA-II, UVB NMPA EU, NMPA)
triazine
Benzylidene camphor sulfonic acid C17H20O4S Mexoryl SL UVB EU, NMPA, and 6%
TGA
Cinoxate C14H18O4 Phlasol, Sundare UVB U.S.FDA, HC, and 3% (U.S.FDA, HC), 6%
TGA (TGA)
Camphor benzalkonium methosulfate C21H31NO5S Camphor benzalkonium sulfate UVB EU, NMPA, and 6%
TGA
4-Methylbenzylidene camphor C18H22O Parsol 5000, Eusolex 6300, Enzacamene UVA-I, UVA-II HC, EU, TGA, and 4%
(partially), UVB NMPA
Diethanolamine methoxycinnamate C14H21NO5 DEA-methoxycinnamate UVB HC 10%
Diethylhexyl butamido triazone C44H59N7O5 Uvasorb HEB, Iscotrizinol UVB EU and NMPA 10%
Diethylamino hydroxybenzoyl hexyl C24H31NO4 Uvinul A Plus UVA-I (partially), EU, TGA, and 10%
benzoate UVA-II NMPA
DromeTRIzole trisiloxane C24H39N3O3Si3 Mexoryl XL UVA-I (partially), HC, TGA, EU, and 10% (TGA), 15% (EU,
UVA-II, UVB NMPA HC, NMPA)
Disodium phenyl dibenzimidazole C20H12N4Na2O12S4 Bisdisulizole disodium UVA-I (partially), EU, TGA, and 10%
tetrasulfonate UVA-II NMPA
Dioxybenzone C14H12O4 Benzophenone-8 UVA-I (partially), U.S.FDA, HC, 3%
UVA-II, UVB TGA
Ethylhexyl triazone C48H66N6O6 Uvinul T 150, Octyl triazone UVA-II (partially), EU, TGA, and 5%
UVB NMPA
Ethoxylated ethyl 4-aminobenzoic C17H27NO7 PEG-25 PABA UVA-II (partially), EU, TGA, and 4% (EU, TGA), 10%
acid UVB NMPA (NMPA)
Ecamsule C28H34O8S2 Mexoryl SX, Terephthalylidene dicamphor UVA-I (partially), HC, EU, TGA, and 10%
sulfonic acid UVA-II, UVB NMPA
(partially)
Homosalate C16H22O3 Homomethyl salicylate (HMS) UVB U.S.FDA, HC, EU, 15% (U.S.FDA, HC),
TGA, and NMPA 10% (EU, NMPA, TGA)
Isoamyl methoxycinnamate C15H20O3 Amiloxate UVA-II (partially), EU, TGA, and 10%
UVB NMPA
Methylene bisbenzotriazolyl C41H50N6O2 Milestab 360, Eversorb M, Tinosorb M, UVA-I, UVA-II, UVB HC, EU, TGA, and 5% (HC), 10% (EU,
tetramethylbutylphenol Parsol Max NMPA TGA, NMPA)
Methoxypropylamino C17H26N2O4 S87 UVA-I EU 3%
Cyclohexenylidene
Ethoxyethylcyanoacetate
Menthyl anthranilate C17H25NO2 Meradimate UVA-I (partially), U.S.FDA, HC, 5%
UVA-II, UVB TGA
Oxybenzone C14H12O3 Escalol 567, Benzophenone-3 UVA-I (partially), U.S.FDA, HC, 6% (U.S.FDA, HC, EU),
UVA-II, UVB TGA, EU, and 10% (TGA, NMPA)
NMPA
Octyl salicylate C15H22O3 Escalol 587, Octisalate UVB U.S.FDA, HC, 5%
TGA, EU, and
NMPA
Octyl methoxycinnamate C18H26O3 Escalol 557, Octinoxate UVB U.S.FDA, HC, 7.5% (U.S.FDA, HC),
TGA, EU, and 10% (EU, TGA, NMPA)
NMPA
Octocrylene C24H27NO2 Parsol 340 UVA-I (partially), U.S.FDA, HC, 10%
UVA-II, UVB TGA, EU, and
NMPA
Phenylene Bis-Diphenyltriazine C36H24N6 TriAsorB UVA-I, UVA-II, UVB EU 5%
Phenylbenzimidazole sulfonic acid C13H10N2O3S Ensulizole UVA-II (partially), U.S.FDA, HC, 4% (U.S.FDA, HC), 8%
UVB TGA, EU, and (EU, TGA, NMPA)
NMPA
Padimate O C17H27NO2 Escalol 507, Ethylhexyl dimethyl PABA OD- UVB U.S.FDA, HC, 8%
PABA TGA, EU, and
NMPA
Polysilicone-15 – Parsol SLX UVA-II (partially), EU, TGA, and 10%
UVB NMPA
Polyacrylamidomethyl benzylidene (C21H25NO2)x – UVB EU and NMPA 6%
camphor
Sulisobenzone sodium C14H11NaO6S Benzophenone 5 UVA-II, UVB EU, TGA, and 5% (EU, NMPA), 10%
NMPA (TGA)
Sulisobenzone C14H12O6S Escalol 577, Benzophenone-4 UVA-I (partially), U.S.FDA, HC, 5% (EU, NMPA), 10%
UVA-II, UVB TGA, EU, NMPA (U.S.FDA, HC, TGA)
(continued on next page)
4
Table 1 (continued )
Name of Ingredients Molecular Formula Other Name Effective Radiation Agencies that Maximum permitted
Range have Approved concentration (w/w)a
Titanium dioxide TiO2 TiO2 UVA-I, UVA-II, UVB U.S.FDA, HC, 25%
TGA, EU, NMPA
Trolamine salicylate C13H21NO6 Aspergel, Aspercreme UVB U.S.FDA, HC, 12%
TGA
Tris-biphenyl triazine C39H27N3 TBPT UVA-II, UVB EU, TGA 10%
Zinc oxide ZnO ZnO UVA-I, UVA-II, UVB U.S.FDA, HC, EU, 25% (U.S.FDA, HC, EU,
TGA, NMPA NMPA), No Limit (TGA)
a
Details are taken from U.S.FDA (http://surl.li/dpyxi), EU (http://surl.li/dpzbc), TGA (http://surl.li/dpzfm), and HC (http://surl.li/dpzga),. UVA-I 340-400 nm
and UVA-II 315-340 nm.
visible and blue light [28]. Phenolic compounds maintain the proper by decreasing erythema production. According to a study topical
structure of the skin by inhibiting elastase and collagenase [29]. They application of caffeine gets metabolized and metabolites increase pho
also remove the free radicals formed due to the reactions in the presence toprotection. Only the presence of caffeine does not enhance SPF but in
of UV rays [30]. Some of the naturally occurring compounds that are the presence of UV filters, it increases SPF that is established by in-vivo as
evaluated for their photoprotection are lignin, rosmarinic acid, marine well as in-vitro study. An in-vivo study performed by Ana Lucía Moro
algae extract, and marine fungal extract [31,32]. S.X. et al. studied the cho-Jácome et al. Caffeine (2.5%) along with physical UV filters such as
ability of a 5% solution of lignin submicrometer particles to improve the titanium dioxide (5.0%) and chemical UV filters such as 3.0% avo
photoprotective effect of a lotion. The results showed that the antioxi benzone (butyl methoxydibenzoylmethane) and 7.5%Ethylhexyl
dant lignin enhanced the SPF by 2.80–3.53. Apart from this, the methoxycinnamate increases SPF from 15.49 to 19.34. Based on the
UVA/UVB ratio for these particles was found to be in the range of result photoprotection against UVB is enhanced in the presence of
0.69–0.72, which demonstrates their potent photoprotective activity Caffeine (2.5%) which increases the SPF up to 25% [40]. Photo
[33]. Rosmarinic acid is a polyphenol that was extracted from the plant protective action and safety of grape pomace extract were determined
P. amboinicus and was evaluated for its UV protective properties. The by Alexandra A. Hübner et al. During the in-vitro study, the synergistic
extract had a peak in both UVA (330 nm) and UVB (229 nm) regions activity of grape pomace extract was evaluated by comparing the
demonstrating the broad-spectrum action of rosmarinic acid. Addition effectivity of emulsion with 10% grape pomace extract and combination
ally, the extract had an SPF of 12.63 [34]. Marine source compounds are of butyl methoxy dibenzoyl methane, ethylhexyl methoxycinnamate,
also an excellent option for natural sunscreen agents. Álvarez-Gómez and ethylhexyl dimethyl PABA as organic UV-filter with an emulsion
et al. conducted a study using two red algae species (Hydropuntia cornea containing only the combination of the organic UV-filters. The study
and Gracilariopsis longissimi). The study demonstrated that these algae reported that grape pomace extract (10%) containing emulsion had
contained mycosporine-like amino acids (MAAs) which had an antiox 17.98% more UVA protection and 20.59% of higher in-vitro clinical
idant property and they prevent 3 out of 10 photons from targeting photo protectivity action than the other emulsion with the absence of
compounds that were UV sensitive. At 13.9 mg/cm2, the highest SPF was adverse reactions such as phototoxicity, sensitization, and irritability
obtained for both the algae, 4.8 for Hydropuntia cornea and 7.5 for [41]. Bamboo extract is full of phenolics and flavonoids which directly
Gracilariopsis longissimi [35]. Another study of SPF evaluation was con reacts with free radicals as well as absorbs the UV light. Katarzyna
ducted using 5,6- Dihydroxyindole-2carboxylic acid (DHICA), a com Barbara Wróblewska et al. compared the photoprotective activity of
pound with structural similarities to melanin precursor, obtained from bamboo extract obtained from the leaves and culm of five native Bra
imperfect non-spore-forming marine fungus Aspergillus nidulans. The zilian species that are M. pluriflora, C. meyeriana, C. capituliflora, C.
pigment had potent UVB protection and antioxidant properties. Also, an bambusoides, and A. aristulata. The bamboo extract was combined with a
SPF of 9.9 was obtained for DHICA [36]. Rutin is an excellent photo 3.0% avobenzone, 7.5% octyl methoxycinnamate, and 8,0% octyl
protective agent due to its antioxidant effect. It is a citrus flavonoid dimethyl PABA. A total of 11 formulations were developed with one
glycoside obtained from plant sources. Letícia Costa Tomazelli et al. being control and the other ten either containing 10% of culm or leaves
performed a comparative in-vivo study regarding the photoprotective as extract from any one species. The in vitro SPF determination results
well as antioxidant effectivity of sunscreen containing rutin and UV showed that after irradiation of UV light the highest SPF was observed
filters like octyl dimethyl PABA and butyl methoxydibenzoylmethane for C. capituliflora culm however, the least differences between SPF value
with only UV-filter based sunscreen. The study reported an enhance before and after irradiation was observed for C. bambusoides leaves
ment in antioxidant properties by 40% as well as photoprotective (before irradiation SPF 36.61 ± 10.68 and after irradiation SPF 35.22 ±
properties by 70%. The in-vivo SPF of 0.1% Rutin-containing sunscreen 13.48). Overall, all the formulations with bamboo remained
was observed 12.4 ± 1.1 whereas it was only 7.3 ± 0.6 for sunscreen broad-spectrum sunscreen after UV irradiation [42]. All these studies
with UV-filters only [37]. Another natural substance ferulic acid which indicate that natural molecules have a lot of potential to be used in a
is a phenolic compound comes under the category of hydroxycinnamic sunscreen formulation.
acids and has a good anti-oxidant effect. Different functional groups in
the structure of ferulic acid are responsible for antioxidant and photo 3. Nanocosmeceuticals
protective effects. The presence of carboxylic acid in the structure of
ferulic acid can give protection against lipid peroxidation, neutralization Currently, cosmetics are one of the growing industries worldwide
of free radicals is possible due to the hydroxyl group attached to ben because of lifestyle changes, pollution, and erratic climate changes.
zene, the vinyl side chain which connects benzene and the carboxylic According to a report, it was believed that the global cosmetic market
group makes the molecule stable, and hydrogen bond between methoxy would reach 805.61 billion USD by 2023, but the growth of the market
substitute and hydroxy group additionally enhances the stability of the was hindered by the COVID-19 outbreak. The market for cosmetics
molecule [38]. According to an in-vivo study performed by Ana Lucía declined in 2020, instead of increasing. As the number of COVID-19
Morocho-Jácome et al. presence of 1.0% ferulic acid along with various cases started decreasing in 2021, the market recovered and was
chemical UV filters such as bis-ethylhexyloxyphenol methoxyphenyl valued at 287.94 billion USD. In the future, the market for cosmetics is
triazine and Ethylhexyl triazine (5.0%) can increase SPF from 19.7 to 26 estimated to be 5% of the compound annual growth rate (CAGR) and
[39]. Another natural substance caffeine gives photoprotection and act will probably reach up to 415.29 billion USD by 2028 [43,44].
5
According to the U.S. FDA, cosmetics are substances that are applied to delivery systems, which improve formulations in various segments, such
the body to enhance attractiveness, cleansing, or beautifying effects as dispersibility, penetration, entrapment, protection, and performance.
without changing any functions or physiology of the body [45]. L’Oreal The following delivery systems are extensively used for sunscreen
S.A., Procter & Gamble Co. (P&G), Johnson & Johnson Services Inc., The formulation: polymeric nanoparticles, nanoemulsions, nanocrystals, sun
Estee Lauder Companies Inc., and Unilever are some of the major players spheres, silica-based nanoparticles, solid-lipid particles (SLPs), nano
in the cosmetic market [43]. carriers, liposomes, transfersomes, ethosomes, transethosomes, nio
Cosmetics and cosmeceuticals are two terms that are utilized inter somes, nanocapsules, hydrogels, and nanosponges [26,54].
changeably by researchers, but in reality, they are different from each Nanosunscreens are better than conventional sunscreens, in many
other. As mentioned earlier, cosmetics do not modify body function and cases because they do not form a chalky white layer over the skin. In
physiology, whereas cosmeceuticals have an active ingredient that is addition, they are odorless and less greasy, so the aesthetic appeal of the
absorbed in the skin to treat the underlying problem by modifying body product is enhanced. As the particles are nanosized, the amount required
function and physiology and making the skin better. Dr. Albert Kligmen to be applied to the skin is also minimized. 4-aminobenzoic acid, TiO2,
in the late 1970s coined the term “cosmeceuticals”. Cosmeceuticals are and ZnO are the most utilized nanoparticles in sunscreens [55,56].
used for improving and preventing various conditions, such as dark General advantages of nanosystems and various nanoparticles used in
spots, dry skin, wrinkles, hyperpigmentation, hair damage, uneven sunscreens are shown in Fig. 3. Furthermore, Table 2 contains the
complexion, photoaging, and sun protection [46]. When nanomaterials method of preparation, pros, and cons of various nanoparticles used in
are used in formulating cosmetics or cosmeceutical products, they are the sunscreens.
called nanocosmetics or nanocosmeceuticals. Nanotechnology is utilized
in formulating a cosmeceutical product because it improves the effi 4. Advanced nanotechnology-based sunscreen formulations
ciency, stability, and bioavailability of the product [47,258,259]. Apart
from that, it also enhances the action time. The nanocosmeceuticals 4.1. Nanoemulsion
have a smaller particle size because of the internal structure rear
rangement, which also enhances their surface area. Some additional These are colloidal formulations that contain nanosized droplets
benefits of nanotechnology in cosmeceuticals are improved adherence dispersed finely in two immiscible liquids. They have high kinetic sta
and coverage [48–50]. bility as the interfacial tension is balanced out using the cosurfactant or
The size of nanoparticles ranges from 1 to 100 nm [51,52]. In surfactant. Nanoemulsion droplet generally have a diameter size range
nanotechnology, various attributes of a compound are observed at the of 100–500 nm [69,70]. Their subtypes are analogous to the conven
nanoscale. The result is used in various science fields such as engi tional emulsion, either biphasic [water in oil (W/O) and oil in water
neering, medicine, optics, food sciences, etc. In several past decades, (O/W)] or triphasic [water in oil in water (W/O/W) and Oil in water in
nanotechnology has delivered several novel solutions for treating oil (O/W/O)]. The portion of the aqueous and oily phase and the type of
various diseases. [53]. There are numerous nanotechnology-based surfactant will influence the structure and potential of the formulation
Fig. 3. Various nanocarriers useful in sunscreen formulations.
6
Table 2
General overview of various types of nanoparticles for sunscreen products and their production method with pros and cons.
Nanoparticles Production method Advantages Disadvantages Reference
Polymeric • Interfacial polymerization • Easily can be utilized in tissue engineering • Presence of toxicity due to the non- [57–59]
nanoparticles • Nano-precipitation • Higher effectiveness over conventional oral delivery biodegradable nature of the polymers.
• Dialysis • Very useful and effective in the case of volatile
• Solvent evaporation substances delivery.
• polymerization of emulsion,
etc.
Nanoemulsion • Hydrogel method • Problems like coalescence and flocculation can be • pH, as well as temperature, can affect the [60,61]
• Microfluidization avoided with nanoemulsions stability
• Ultrasonication Non-irritant as well as non-toxic nature of these molecules • A higher amount of surfactant is required
• High-pressure homogenization enhances their topical use to maintain stability.
• Phase inversion temperature • Due to oil soluble nature of the molecules, it can be
• Phase inversion point etc. useful in the toxicity study of oil-soluble substances
• With the small size of these molecules, a higher
penetration rate across the skin can be achieved.
Nanocrystals • Combinational technology • Most likely for hydrophobic substances • Not suitable for substances that are [62]
methods • Enhances drug solubility and permeation hydrophilic in nature.
• Bottom-up and Top-down
methods
• High-pressure homogenization
techniques etc.
Mesoporous silica • Sol-gel method • Major advantages related to their excellent • Leads to melanoma. [63]
particles • Evaporation through the self- biodegradable nature as well nontoxic nature.
induced assembly.
Solid lipid • Double emulsion method • Excellent biodegradable property • Low drug encapsulation property [62,64]
nanoparticles • Cold as well as hot • Easy to produce • Solution state stability issues.
homogenization method • Higher bioavailability of drug due to better skin
• Ultrasonication method permeation property.
• Microemulsion method
• Melt dispersion method etc.
Nanostructure lipid • Membrane contactor method • Higher physical stability • Surfactant-induced irritancy [65]
carriers • Microfluidization method • Easy to formulate • Cytotoxic effect of lipid portion.
• Phase inversion method • Higher drug loading capacity
• Solvent injection method • Higher penetration
• Cold as well as hot • Excellent value of benefit/risk ratio
homogenization methods • Controlled drug delivery property
• Solvent emulsification
diffusion
• Solvent emulsification
evaluation etc.
Liposomes • Extrusion method • Act as a nanocarrier for hydrophilic as well as • It may be allergic in some cases [58,66]
• Sonication method hydrophobic drugs • Lesser stability
• Solvent injection method • Excellent biodegradable property
• Supercritical fluid method • Can produce longer action through sustained release
• Heating method
• Bubble method
• Film hydration method etc.
Niosomes • Microfluidization • Higher bioavailability due to a higher rate of penetration • More complex as well as time-consuming [62,67,
• Ether injection method • Higher drug loading capacity preparation 68]
• Sonication • Higher physical stability. • Highly costly in terms of production
• Bubble method .
• Handjani-Vila method
• Handshaking method
• Enzymatic method
• Lipid injection method
• Single pass method etc.
to entrap the molecule, i.e., hydrophilic or lipophilic molecules [71]. Nanoemulsions have various advantages, such as easy stratum cor
Apart from this, the surfactant is also essential, as it affects numerous neum penetration, small size, control delivery possible, transparency or
formulation factors, such as nanoemulsion and skin interactions and transposition, reduced water loss, skin texture, pleasing sensation, ste
nanoemulsion physical stability [72]. One of the most commonly used reochemical stability, and rapid absorption [76]. Additionally, its
surfactants is Poloxamer 188, which is nonionic in nature. Nano components are considered generally recognized as safe (GRAS) by the
emulsions are usually liquid, but when their structure is modified, by U.S.FDA. Nanoemulsions are generally biodegradable and soluble, and
changing the method of preparation, numerous different products can the products formed after their degradation are also safe. Cosmetic
be developed, for example, water-like gels [73]. Some of the most widely application of nanoemulsions has surged due to various reasons, such as
used preparation methods for O/W nanoemulsions are homogenization, high solubilization of lipophilic molecules, easy absorption in skin due
spontaneous nanoemulsification, phase inversion composition, and to high viscosity, low surfactant concentration, and droplet size con
phase inversion temperature [74,75]. A study reported that as the size of trolling ability [69,71,73,77–79]. Various studies of NEs are given in
the droplet depletes, the stability of the system increases, an essential Table 3.
factor that affects active substance loading. The study also describes that
for the optimal droplet size, homogenization is the best method, but the
only disadvantage is the high pressure needed [73].
7
Table 3
Research summary of various nanoparticles evaluated for sunscreen formulations.
Nanoparticles Method of preparation Composition Entrapment Study results References
efficiency (EE)
%
PNs of morin [SC8 Solvent evaporation and modified SC8: Morin, solution of PVA, PLGA, ZnO, TiO2 12.27 Skin irritation study: - [80]
and SC5] double emulsion method. and avobenzone. Nonirritating
SC5: Morin, solution of PVA, TiO2, PLGA and In vitro SPF:
ZnO. For SC8: 42.32 ± 4.29
For SC5: 41.66 ± 4.51
Skin deposition:
For SC8 formulation -
178.15 ± 7.44 μg/cm2
175.66 ± 6.09 μg/cm2
Skin permeability study:
43.91 ± 4.01 μg/cm2
For SC5 formulation –
Q12 = 44.1 ± 3.15 μg/cm2
PNs of naringenin Solvent evaporation and single PVA solution, naringenin, and PLGA. 32.45 Skin irritation study: - [81]
(NN5) emulsion method. Nonirritating
In vitro SPF of
naringenin loaded PNs:
27.02 ± 0.62
Skin deposition:
10.38 ± 0.48 μg/cm2
Skin permeability study:
Q12 = 184.03 ± 3.37 μg/
cm2
PNs of OCR and ZnO miniemulsion polymerization ZnO, OCR nanoparticles, polysorbate 20, PMMA/ For ZnO: 96 In vitro SPF: 32 ± 5 [82]
method. PS, propylene glycol, VP copolymer/ammonium and for OCR: 97
acryloyldimethyltaurate, an aqueous solution of
methylisothiazolinone, and distilled water.
SLNs of urucum oil High-pressure homogenization OMC, urucum oil, Hydroxyethylcellulose, – Skin irritation study: - [83]
and OMC method. sodium lauryl sulfate, glyceryl monostearate, Nonirritating
methylisothiazolinone/ In vitro SPF:
methylchloroisothiazolinone, and water. 21.07 ± 1.2
SLNs of silymarin A mixture of the microemulsion Silymarin, polysorbate 80, chloroform, glyceryl 92.36 Skin irritation study: - [84]
(F6) method and sonication method. monostearate, methanol, and distilled water. Nonirritating
In vivo SPF: 14.07
In vitro SPF: 13.80
Skin permeability (Ex
vivo) study: 86.50%
(After 8 h) in albino rat
skin
SLNs of OCR and ZnO Hot emulsion method. SLNs of OCR: OCR, tripalmitin, and polysorbate SLNs of OCR: – [85]
80. 98.98
SLNs of ZnO: SLNs of ZnO:
ZnO, tripalmitin, and polysorbate 80. 96.18
NEs of OMC with Ultrasonic processing method OMC, chitosan, sorbitan oleate, polysorbate 80, – Skin permeability study: [86]
chitosan and methylisothiazolinone/phenoxyethanol, and (Following data are after
without chitosan distilled water. 6 h of skin deposition)
In epidermis
Chitosan containing NEs
of OMC: 2.28 ± 0.25%
Only NEs of OMC: 0.89 ±
0.08%
In dermis
Only NEs of OMC: 0.92 ±
0.11%
Chitosan containing NEs
of OMC: 0.87 ± 0.06%
CA containing NEs Spontaneous nanoemulsification CA, sorbitan oleate, ethyl oleate, ethoxydiglycol, 99.02 ± 0.13 Skin irritation study: - [87]
(CA-NE4 was the method and aqueous solution. Nonirritating
optimized Skin permeability study:
formulation) - 96.62% (After 24 h)
NEs of Parsol MCX Spontaneous nanoemulsification C12-15 alkyl benzoate, polysorbate 80, BMDBM, NEs with – [88]
and Parsol 1789 method α-tocopherol, sorbitan oleate, ethylhexyl Parsol MCX:99
methoxycinnamate, and aqueous solution. NEs with
Parsol 1789:
99
TRFs of HA and EGCG Modified thin film hydration method EGCG, HA, sodium cholate, and Soy For EGCG: Skin deposition: [89]
(ETF20) along with high-pressurized phosphatidylcholine. 76.53 ± 2.68 38.90 ± 1.16 μg/cm2
homogenization For HA: 48.57 Skin permeability study:
± 4.35 Q12 = 199.1 ± 6.30 μg/
cm2
8
efficiency (EE)
%
TRFs of C. longa Modified lipid film hydration Sodium deoxycholate, lecithin, and extract of 84.1 ± 0.05 – [90]
extract method C. longa (2%).
TRFs of vitamin E and Combination of active substances Vitamin E, caffeine, sodium cholate, soybean TRFs of vitE: – [91]
caffeine with the mixture of soybean phosphatidylcholine, and purified water. 62.297 ± 5.176
phosphatidylcholine, surfactant TRFs of caf:
along with purified water 4.607 ± 0.910
ETSs of C. longa Cold method Extract of C. longa (2%), ethanol, l- 72.5 ± 1.3 – [90]
extract α-phosphatidylcholine (95% Soy), and water.
ETSs of vitamin E and Cold method Vitamin E, caffeine, ethanol, soybean ETSs of vitE: – [91]
caffeine phosphatidylcholine, and purified water. 81.558 ± 7.806
ETSs of vitE
and caf: 2.608
± 0.223
TESs of vitamin E and Combination of the cold method Vitamin E, caffeine, sodium cholate, soybean TESs of vitE: – [91]
caffeine along with TRFs of vitamin E and phosphatidylcholine, ethanol, and purified 80.715 ± 2.783
caffeine preparation water. TESs of vitE
and caf: 3.636
± 1.158
NLCs of BMDBM Melt emulsification method along Glyceryl stearate as well as cetyl palmitates like 80–86.5 In vivo EUVA-PF: 30 [92]
with a higher shear homogenization solid lipids, squalene as well as medium-chain
process triglycerides like liquid lipids, lecithin,
polysorbate 80, polysorbate 20, BMDBM, and
poloxamer 188.
Mixtures of Organic homogenization process under hot Ethylhexyl triazone, ethylhexyl – In vitro SPF: 20.19 ± 1.03 [93]
UV filters loaded and high-pressure methoxycinnamate, bis-ethylhexyloxyphenol
NLCs (formulations methoxyphenyl triazine, Decyl glucoside, and
of carnauba wax) carnauba wax.
MSNs with PMOBTB, Condensation in a basic aqueous Precursors of silica TEOS, BTE, and BTB, – In vivo SPF: [94]
and PMOBTE of medium of precursors of silica like cetyltrimethylammonium bromide, avobenzone, For PMOBTB: 18.5 ± 0.2
avobenzone BTB, BTE, and TEOS in presence of and Zn2+. For PMOBTE: 9.1 ± 0.1
CTAB (mesopore-templating For MSNs: 1.2 ± 0.1.
surfactant) The ratio of UVA/UVB:
For PMOBTB: 0.72
For PMOBTE: 0.9
For MSNs: 0.74
NCs loaded with Interfacial polycondensation and C12-15 alkyl benzoate, diethylenetriamine, Parsol 1789 Ex vivo SPF [88]
Parsol MCX and spontaneous nanoemulsification sebacoyl chloride, α-tocopherol, BMDBM, and loaded NCs: Parsol MCX and Parsol
Parsol 1789 ethylhexyl methoxycinnamate. 98.33 ± 0.92 1789 loaded NCs:
Parsol MCX 3.97 ± 0.84
loaded NCs: Parsol 1789 loaded NCs:
98.18 ± 0.67 1.39 ± 0.41
Parsol MCX loaded NCs:
3.11 ± 0.76
Cin-CNCs Esterification method CNCs, water (demineralized), and cinnamoyl – In vitro SPF: 20.3 [95]
chloride.
Nanocrystals of Pretreatment followed by Apigenin. – – [96]
apigenin application of a high-pressure
LIPs of C. longa Lipid film hydration method Extract of C. longa (2%), cholesterol, and l- 46.8 ± 1.4 – [90]
extract α-phosphatidylcholine (95% Soy).
LIPs of OMC Thin lipid film hydration OMC, α-tocopherol, phosphatidylcholine, and 84.97 ± 2.02 Skin irritation study: - [97]
cholesterol. Nonirritating.
After 240 min deposition
in tape stripping: 22.64
± 7.55 μg/cm2
Before immersion In vivo
study: 11.5 ± 2.7
After immersion In vivo
study: 5.8 ± 1.4
In vitro SPF:
13.88 ± 0.07
β- cyclodextrins and OMC loaded β-CD: kneading OMC loaded β-CD: β-cyclodextrin and OMC. OMC loaded In vivo SPF of [98]
LIPs of OMC method OMC- loaded liposome: β-CD: 89.0 OMC loaded β-CD: 8.5
OMC- loaded liposome: film OMC molecule, phosphatidylcholine, and OMC- loaded OMC loaded liposome:
hydration cholesterol. liposome: 11.0 ± 1.3
88.88 Combination of OMC
loaded β-CD and OMC-
loaded liposomes: 11.6
± 1.6
Postimmersion for OMC-
± 2.2
Postimmersion for OMC
loaded β-CD: 6.5
Postimmersion for the
9
efficiency (EE)
%
combination of OMC-
loaded β-CD and OMC-
EE = Entrapment efficiency = Incorporated drug’s weight/drug’s weight at the initial of experiment × 100. PNs = polymeric nanoparticle; PLGA = poly(glycolic-co-
lactic)acis; PVA = polyvinyl alcohol; OCR = octocrylene; ZnO = zinc oxide; PMMA/PS = polystyrene-co-methyl methacrylate; SLN = solid lipid nanoparticle; OMC =
octyl-methoxycinnamate; NE = nanoemulsion; CA = catechin; TRF = transfersome; HA = hyaluronic acid; ETS = ethosome; EGCG = epigallocatechin-3-gallate; TES =
transethosome; NLC = nanostructured lipid carrier; BMDBM = butyl-methoxydibenzoylmethane; EUVA-PF = erythemal UV-A protection factor; MSN = mesoporous
silica nanoparticle; PMOBTE = periodic mesoporous organic with ethane bridge; CTAB = cetyltrimethylammonium bromide; PMOBTB = periodic mesoporous organic
with benzene bridge; TEOS = tetraethoxysilane; BTE = 1,4-bis(triethoxysilyl)ethane; CNC = cellulose nanocrystal; NC = nanocapsule; Cin-CNC = cinnamate-func
tionalized cellulose nanocrystal; LIPs = liposomes.
4.2. Sunsphere 4.3. Transfersomes
In 1994, for the first time, the concept of a sunsphere came into the Transfersomes (TFs) are modified versions of liposomes that are
market. With the increase in the worldwide temperature and diseases made by adding an edge activator or surfactant to the lipid bilayer of
associated with sun rays (skin-related problems), the Rohm and Haas liposomes. Some of the most widely used surfactants for transfersomes
Company formulated one novel structure with excellent photoprotective are dipotassium glycyrrhizinate, sodium cholate, Tween 20, Span 60,
properties. Sunsphere enhances the SPF of the sunscreen formulation and sodium deoxycholate [102]. They range from 100 to 150 nm and are
with scattering and refraction of the UV rays by altering the protective the first generation of ultradeformable vesicles (UDVs) [103]. The two
layer beyond the skin. It consists of an approximate size of 325 nm with a main advantages of transfersomes over liposomes are greater deform
copolymer of acrylate or styrene [99]. The use of different inorganic, as ability and flexibility. The preparation methods are analogous to lipo
well as organic UV filters along with the sunspheres, are used exten somes; however, the two most extensively used methods are vortexing
sively in sunscreen formulations. The sunspheres have water inside the sonication and rotary evaporation sonication (thin film hydration
sphere which moves out and is replaced by air when they are applied on method) [104]. TFs have a special ability to modify/deform their
the skin, this is possible because they are developed through emulsion structure, which makes their easy penetration and permeation from the
polymerization. Different layers contain different refractive index (RI) stratum corneum (SC) by passing through narrow intercellular spaces.
properties, so when sun rays reach the skin, they need to pass through Apart from this, when the water of the formulation is evaporated, this
various layers, such as a layer of copolymers (RI is 1.6), a dry layer of forms an osmotic gradient (on the SC, which is in contact with air,
sunscreen (RI is approximately 1.4–1.5), and only air containing sun 1030%–75% in the viable epidermis) that acts as a driving force and aids
spheres/vacuum containing sunspheres (RI is 1) [100]. in formulation permeation. All of these factors enhance the delivery of
During the scattering and reflection processes across the sunscreen active ingredients to the desired site, which can be either the epidermis
film layer, the absorption mechanism of sun rays takes place through UV or dermis. TFs can transport both hydrophilic and lipophilic ingredients,
filters present in the sunscreen cream along with the sun spheres. Sun but while delivering hydrophobic/lipophilic components, the vesicles
spheres do not absorb UV radiation like UV filters (As shown in Fig. 4). cannot maintain their shape and flexibility. Nonocclusive conditions are
Maximum UV light scattering is obtained because of the tremendous a prerequisite for this formulation [91,102,105,106].
outer nanostructure and maximized interior of the sunsphere molecule. Hyaluronic acid (HA) is an essential connective tissue component
There are many advantages, such as good compatibility with the various that is present in the extracellular spaces and assists in maintaining
UV filters, without any toxic effects or side effects. It is more beneficial hydrated, smooth, and elastic skin [107]. A study combined it with
with the other ingredients of the sunscreens, which are facing resistance epigallocatechin-3-gallate (EGCG) (a natural antioxidant presents in
toward the water. The main property of the sun sphere is the boosting or large quantities in green tea) in transfersomes and evaluated their
enhancement effect in the SPF index of any sunscreen formulation with antiaging, antioxidant, and UV protection properties [89]. The results
the use of UV filters, and this is well established by various experiments showed that in the human keratinocyte cell line, the transfersomal
being performed to test the role of the sun spheres in sunscreen for formulation was able to reduce the production of reactive oxygen spe
mulations. Octyl methoxycinnamate (OMC), which is a wonderful UV cies (more details are given in table 03. Yamaguchi et al. [108] and
filter when combined with sunspheres, enhances the SPF of the formu Ramos-e-Silva et al. [109] demonstrated that UV exposure elevates
lation. It is also well established in one study that sunspheres alone oxidative stress, which leads to an increase in ROS generation, a
(without UV filters) do not absorb UV radiation. In the study, it has been decrease in skin hydration, and a reduction in sebum production. To
proven that when a sunsphere is used without UV filters in in-vivo overcome this issue, various creams containing Curcuma longa’s alco
testing, the SPF value is under 2, and as per the U.S.FDA final OTC holic extract were prepared by Kaur et al. Curcuma longa has curcumi
monographs, it proves that sun spheres are not absorbing UV radiation noids that have antioxidant properties [90]. First, this extract was
and cannot improve the SPF without combination with UV filters. In incorporated into ethosomes, transfersomes, and liposomes, and later,
another in vitro testing method, it was established that the use of 4% these vesicle systems were added to creams (detailed specifications
sunspheres along with 1% OMC increased the SPF value of the formu given in Table 3). Out of the three, the tranferosome-based cream was
lation to 12 times higher than the use of only 7.5% OMC. Sunsphere also the most effective. The study suggested that the lipids in the vesicles
does not affect the skin adhesion for the water resistance formulations. provided a moisturizing effect and that Curcuma longa extract provided
When two formulations containing 7.5% OMC, 3% octyl salicylate, and photoprotective activity.
2% oxybenzone along with 5% sunspheres and another formulation
containing 6% OMC, 1% oxybenzone along with 5% sunspheres were 4.4. Ethosomes
used in an in vitro experiment observed under an optometric SPF
analyzer at 45 ◦ C for a 3-month enhancement in the SPF of two for These are also types of UDVs that contain three ingredients: water,
mulations up to 70% and 60%, respectively [101]. Additionally, other ethanol, and phospholipids. These are named ethosomes because
studies are mentioned in Table 3. ethanol is their main constituent, with its composition varying between
10
Fig. 4. Impact of sunscreen formulations. (a) shows the mechanism of the sun-protecting effect of the sun sphere-containing formulation along with UV filters. (b)
shows the comparison of the effects before and after the use of the sunscreen formulations.
20 and 45% [91,110]. While the concentration of phospholipids ranges Bilayer-bound ethanol facilitates the deformation of the ethosomes. To
between 0.5 and 10%, pure and hydrogenated phosphatidylinositol, prepare this system, the lipids and active ingredients are first dissolved
phosphatidylethanolamine, and phosphatidylcholine are some of the in excess of ethanol, and then at constant flow, water is mixed. Some
phospholipids that are most widely used in ethosome preparation [111]. main ethosome preparation methods are REV and film hydration
Natural, semisynthetic, or synthetic phospholipids are utilized for methods [112–114].
ethosome preparation. So, ethosomes are basically liposomes with some Ethanol interacts with the hydrophilic region of lipids present in the
ethanol which is bound to the bilayer or present in the aqueous phase. SC and decreases their melting point. In this way, ethanol enhances cell
11
permeability and phospholipid bilayer fluidity. Under nonocclusive formation of a lipidic bilayer of phospholipids, while many natural
conditions, ethanol evaporates after the application of ethosomes. phospholipid derivatives are also being used, such as phosphatidyleth
However, the active compound is released under both conditions anolamine, phosphatidylserine, phosphatidylinositol, phosphatidylgly
(occlusive or nonocclusive). To date, the mechanism of ethosomes is not cerol, and phosphatidylcholine (which contain skin softening
completely understood, but studies have shown that the interaction of properties) [67]. Enhancement in the stability of the lipidic layer can be
ethosomes with the lipid bilayer, their elasticity, and SC lipid bilayer obtained by using cholesterol molecules along with phospholipid mol
disruption by ethanol work synergistically. Compared to hydroalcoholic ecules [97,98]. There are several methods by which we can prepare li
solutions and liposomes, the active molecules permeate the skin better posomes, such as reversed-phase evaporation (REV), detergent dialysis,
with ethosomes. They can be used for both lipophilic and hydrophilic the Bangham method (hydration of lipidic layer/film), the solvent in
compounds. However, the presence of ethanol favors lipid substances jection method, supercritical reversed-phase evaporation, and
and enhances their solubility, which leads to a higher entrapment effi freeze-drying [122].
ciency. Hence, they are preferred for lipophilic molecules [112,115]. On the application of sunscreen formulations containing liposomal
In sunscreens, ethosomes are used for delivering vitamin E in the structures above the skin, it remains in the subcutaneous layer of the
deeper layers of the skin. Vitamin E prevents sunlight-induced malig skin “because of various complexities in the SC layer, including hair
nancies by inhibiting ROS, but it has insufficient skin permeability and follicles” and generates a reservoir system of drug release. Ultimately, all
accumulation. Godin and Touitou studied the penetration of vitamin E- these reservoir structures form-controlled release of the drug from the
loaded liposomes and ethosomes in fibroblasts. They reported that the liposomes [123,124]. During the formulation of sunscreen creams using
ethosomal nanosystem had approximately 3.5 times higher penetration liposomes, UV filters are very important substances that need to be
than the liposomal nanosystem (More details given in Table 3) [116]. incorporated into the lipidic bilayer of liposomes. Many studies have
shown better efficacy as well as safety by using liposomes in sunscreen
4.5. Transethosomes formulations. In one study, Mota Ade et al. established that the use of
octyl methoxycinnamate (OMC) by encapsulating it into liposomes
Transethosomes are a combination of transfersomes and ethosomes shows a higher Sun Protection Factor (SPF) in an in vivo study compared
that contain water, phospholipids, edge activators/surfactants, and to its free octyl methoxycinnamate (without liposomes) containing for
ethanol (up to 30%). They are irregular spherical-shaped UDVs (ultra mulations. Furthermore, in the assay using technetium 99 m, deep
deformable vesicles) that have been developed recently. Compared to penetration, as well as entrance into the systemic circulation of mole
ethosomes and transfersomes, they have higher skin permeation and cules such as OMC, can be prevented by using liposomes in sunscreen
elasticity. They are the most flexible UDVs because the association of formulations. Another study by Monteiro et al. shows a comparison
surfactant and ethanol rearranges the lipid bilayer. For their prepara study of OMC with liposomes, only OMC formulation (free formulation),
tion, the Flim hydration technique is utilized; the same method used for OMC with beta-cyclodextrin, and the last OMC with both liposomes and
the production of ethosomes only uses organic phases that are not beta-cyclodextrin. After the study, Monteiro et al. concluded that OMC
identical. Large-scale production of transethosomes is easy; hence, they with liposomes shows better in vitro permeation, in vivo water resistance,
become vesicles of choice for industrial purposes [91,117–119]. Trans and SPF along with better photoprotective effects. Xu et al. also
ethosomes have another advantage over ethosomes and transferosomes concluded after a study that combinations of UV filters with the lipidic
due to their higher deformability ability. This quality is due to the moiety of liposomes enhance the photoprotection of the formulations.
presence of ethanol and surfactant. The completion of studies on the skin More details related to the studies are given in Table 3
permeability and penetration capacities of various UDV-containing
structures of transethosomes shows very good results, especially for 4.7. Niosomes
vitamin E-containing transethosome preparations (Study detail in
Table 3). The entrapment efficiency of the preparation was measured In cosmeceuticals, many formulations are available with a tremen
through the high-performance liquid chromatography (HPLC) method. dous effect on external applications to the human body. Currently, to
Among all the study parameters, transethosomes showed better perfor overcome many problems related to skin permeability and the efficacy
mance along with deeper penetration in the skin layers [91]. of sunscreens, novel approaches such as niosome-containing prepara
tions have been adopted by manufacturers. Niosomes are used as car
4.6. Liposomes riers in formulations, which ultimately enhances the effectiveness of
drugs that cannot easily cross the complex structure of the skin [125].
Liposomes are vesicular types of nanocarriers with a spherical shape Niosomes are single-chain structures containing a nonionic surfactant,
consisting of a phospholipidic bilayer along with a hydrophilic core with cholesterol with polyethylene glycol, and drugs inside vesicles with an
a size range of 20 nm–100 nm. Liposomes can carry or increase the ideal size range between 100 nm and 2 μm [126,127]. Nonionic sur
effectiveness/permeation of hydrophilic as well as hydrophobic drugs factants enhance the efficacy and stability of niosomes along with their
across the layers of the skin [120]. Hydrophilic substances can be carried excellent properties of being biodegradable, biocompatible, and
through an aqueous core, and hydrophobic substances can be carried nontoxic in nature toward the skin. Cristal Cerqueira et al. prepared
through a phospholipid bilayer [121]. This is a major advantage of li niosomes-based sunscreen that had shown entrapment efficacy above
posomes with minimum adverse reactions in drug delivery for a specific 45% and the SPF was above 34. In addition to that, the formulation was
purpose in sunscreen formulations. It is biodegradable and biocompat not toxic when tested in macrophages. Overall, the study demonstrated
ible in nature, with accurate and effective drug penetration along with the potential of niosomes as a carrier option in a sunscreen formulation.
reduced irritation of the skin. An increase in the use of these novel ap [128]
proaches might be due to an excellent advantage that is due to the
different components in their structure. The lipidic bilayer prevents the 4.8. Nanosponges
leakage of hydrophilic drugs/substances present in the vesicle. Double
chain phospholipids and cholesterol are the main part of the lipidic Nanosponges are the newly preferred carrier molecule in the cos
structure in liposomes, and according to the number of layers and size of meceutical branch along with sunscreen formulations. It contains a
liposome structure, they are further classified into three types: 1) small nanosized small cavity by which it carries the hydrophilic as well as
size with unilamellar vesicles, 2) large size with unilamellar vesicles and lipophilic drug moiety present in the formulations. The main advantage
3) multilamellar vesicles [26]. Phospholipids such as dimyristoyl of using these molecules is that they have excellent entrapment effi
phosphatidylcholine are examples of synthetic phospholipids used in the ciency as well as tremendous controlled release properties, which
12
ultimately enhance the effectiveness of the drug substances. Nano active molecules if they have poor solubility in the lipid core. Addi
sponges are mesh-like three-dimensional structures made up of tionally, as the active ingredients are loaded into an improper SLN lipid
degradable polyesters. It is a combination containing polyesters with matrix, they start to release early [83,84,93,137,138].
cross-linkers that can be prepared through various methods, such as the Silybum marianum (milk thistle) contains the polyphenol silymarin,
quasi-emulsion solvent diffusion method and liquid-liquid suspension which has photoprotective and antioxidant properties. Sunscreens con
polymerization [126]. taining silymarin SLNs were prepared and evaluated for their photo
protective action by Netto and Jose (details in Table 3). The silymarin
4.9. Hydrogels SLNs showed a tremendous photoprotective effect with an in vivo SPF of
14.1 and an in vitro SPF of 13.8. Moreover, the accelerated stability study
Hydrogels are another new approach currently used in various of the sunscreen demonstrated no notable effects on the parameters.
cosmetic preparations, including sunscreen formulations. The excellent This result suggests that SLNs have great potential to carry photo
structure of hydrogels in sunscreen formulations gives cooling effects protective agents and that silymarin has the potential to replace syn
along with UV protection. Hydrogels contain a very complex network thetic UV filters [84].
structure in which drug molecules are present with cross-linkages and In one of the studies, organic and inorganic UV filter combinations
contain a high amount of water in the matrix. Hydrogel-based sunscreen and SLNs’ photoprotective properties were evaluated. SLNs were
formulations containing tannic acid as well as hyaluronic acid give incorporated with OCR and ZnO UV filters and then formulated into a
excellent broad-spectrum UV-protecting effects against UVA and UVB suspension [85]. Then, the UV-blocking properties were evaluated and
rays. The cooling effect along with sun protection is primarily due to the compared for SLN-loaded suspensions and suspensions without SLNs.
watery part of the structure of the hydrogel moiety. Recently, various The physical state of SLNs was evaluated by stability studies for a year at
studies and their results in the literature suggested that by mixing two or 4 ◦ C, 25 ◦ C, and 40 ◦ C. After that, the SLNs were analyzed by X-ray
more substances, it can be prepared very easily, which ultimately gives powder diffraction (XRD), differential scanning calorimetry, Fourier
good adhesion to the skin and contains other properties, such as anti transform infrared spectroscopy (FT-IR), and nuclear magnetic reso
oxidant activity along with UV protection [129]. nance. The analysis showed a lack of stability issues. Apart from stability
studies, pH was also determined periodically. It was in the range of
4.10. Solid lipid nanoparticles 5.4–5.9 with minor fluctuations. In addition, it was reported that
loading efficacy and lipid crystalline structure were two essential factors
Solid lipid particles were discovered in the 1990s, away later than that govern the long-term retention or expulsion of active ingredients.
other conventional vesicular nanosystems. They range from 40 to 1000 The in vitro Transwell test depicted that SLNs incorporated with UV
nm in size and are spherical in shape [103]. It has an inner lipid core that filters have a synergistic photoprotective effect, and SLNs alone can also
is solid at room temperature and an outer lipid layer. The lipids utilized block UV rays. The results also illustrate that octocrylene (OCR) SLNs
for solid lipid nanoparticles (SLNs) are waxes, ceramides, steroids, fatty have higher absorption in the UVB region, whereas ZnO-loaded SLNs
acids, and glycerides which are analogous to lipids present in the skin have greater absorption in the UVA region [85].
[130]. To prepare SLNs in an aqueous solution, the lipid molecules are
dispersed in the presence of a surfactant. For this, homogenization [103] 4.11. Nanostructure lipid carrier
is commonly preferred, but according to size, function, and encapsulated
molecule, other methods, such as double emulsion [131], spray drying Nanostructured lipid carriers are analogous to solid lipid nano
[132], or ultrasonication [133], can also be utilized. particles and were designed to overcome the disadvantages of SLNs.
SLNs are favoured for the delivery of lipophilic substances, as they They are second-generation lipid-based nanostructures that have a
can be easily incorporated between the fatty chains, dispersed into the mixture of solid lipids and liquid at the core instead of only solid lipids
core, or into the lipid layer. Apart from the lipophilic substance, hy such as SLNs (at room temperature). Mono-, di-, or triglyceride lipids of
drophilic substances such as proteins and peptides can also be trans natural and synthetic origin should be used as organisms to tolerate
ported, but for this, two surfactants are used (one hydrophobic and the them well [93,103]. NLCs and SLNs have an identical method of prep
other hydrophilic) that assist in the encapsulation of the hydrophilic aration and components, but the crystalline structure of NLCs is more
substance in an inner aqueous phase [131,134–136]. This finding por irregular and amorphous than that of SLNs due to the mixture of
trays the crucial role of surfactants in SLN preparation. SLNs have the different physical states and lipids [93]. The main advantages of NLCs
following: higher stability in hydrophilic and lipophilic environments, are their high loading capacity and the prevention of active molecules
enhanced stability of active ingredients that are labile, prevention of released during storage. These properties are due to different compart
side effects that are due to high doses, occlusive properties, control ments in the lipid matrix that are formed by the irregular structures of
release at the target site, tremendous biodegradability and tolerability the NLCs. NLCs can transport both hydrophilic and lipophilic com
(as the lipids used are analogous to physiological lipids that have low pounds, but lipophilic compounds are preferred [131,135,136]. NLCs
toxicity). Control release can be achieved by modifying the combination are extensively used in cosmetics due to their ability to stabilize active
of the lipids and fatty acids utilized in the SLN structure [83,137]. molecules, occlusive properties that enhance bioavailability and great
For sunscreen formulations, SLNs are ideal because they possess UV- skin hydration, and high skin adherence. In sunscreen, NLCs are widely
blocking and photoprotective properties. The high degree of crystalli used because they decrease the frequency of applications and enhance
zation of the SLN lipid structure confers these properties. When UV fil skin residence time [93,138,139].
ters are incorporated into them, they act synergistically, and enhanced A mixture of ethylhexyl triazone, ethylhexyl methoxycinnamate, and
UV protection is obtained because a lower concentration of UV filters is bis-ethylhexyloxyphenol methoxyphenyl triazine (organic UV filter)
needed, and the chances of toxicity are significantly reduced. Addi was incorporated into NLCs by Nikolic et al. These NLCs were prepared
tionally, SLNs give occlusion effects and form a smooth film on the skin using different solid lipids to evaluate their stability. Numerous prop
surface, which is hard to achieve for occlusive oils (e.g.paraffin). erties of NLCs, such as UV absorbance, stability, physical state, size, and
Penetration of the active molecules becomes slow due to the lipid film, shape, were measured and compared to a conventional NE. After that,
which reduces their toxicity and enhances UV resistance. Despite these were formulated into the hydrogel, and their in vitro SPF was
numerous advantages, SLNs have some concerning problems related to determined. Compared to the reference NE and the NLCs with beeswax,
the release of the active ingredient during storage. The degree order of the NLCs with carnauba wax showed 45% higher UV absorbance and in
SLN crystals increases after solidification when solid lipids crystallize in vitro SPF (in vitro SPF of NLCs with carnauba wax 20.19 ± 1.03, in vitro
higher energy forms (a or b) [138]. This causes improper loading of SPF of NLCs with beeswax 14.13 ± 1.33, reference NE’s in vitro SPF
13
13.76 ± 1.44). This proved that the choice of solid lipid is crucial; into the systemic circulation. In addition, their cytotoxic study per
carnauba wax has a solid shell structure that scatters radiation and aids formed in vitro in HaCaT cells did not show any toxicity. Their safety for
in photoprotection synergistically with the active molecule. NLCs are daily application was established by analyzing their accumulation in the
distributed nonuniformly on the skin; to overcome this problem, skin after cream application for one day, and the results showed the
hydrogels were used. Their stability was confirmed by X-ray powder absence of naringenin-loaded PNs [80,81,156].
diffraction (XRD). When a high concentration of active ingredients is The organic UV filters can enter the systemic circulation by pene
used, the spreadability is not maintained; hence, NLCs can be used for trating hair follicles and the skin. To prevent this, the PNs were modi
formulations with SPF up to 30 [93]. fied, and polymeric bioadhesive nanoparticles (BNPs) were prepared.
In one of the studies, NLCs were prepared for butylmethox BNPs prevent UV filters from penetrating deeper skin layers and keep
ydibenzoylmethane (BMDBM), a UV-A blocking organic filter with poor them on the skin surface through their bioadhesion property. BNPs also
photostability, to enhance their photostability (details in Table 3). For reduce the production of ROS that cause DNA damage. A study con
this, two solid lipids (cetyl palmitate and glyceryl stearate) and two ducted by Deng et al. describes these advantages. In this study,
liquid lipids (medium-chain triglycerides and squalene) were used with padimate-O-loaded BNPs were compared with simple form padimate-O
0.5%, 1%, or 1.5% concentrations of BMDBM. In vivo, the erythemal that was not encapsulated with bioadhesive particles. The study re
UVA protection factor (EUVA-PF) was determined using Transpore tape ported that the padimate-O loaded in BNPs did not penetrate the skin
and compared to conventional nanoemulsions with an equivalent and remained on the surface, due to which DNA double-strand breaks
amount of BMDBM of nearly 30 times. In addition, more than 96% of the were reduced significantly. Moreover, BNPs reduce the UV filter con
UV-A rays were absorbed. After 3 h of UV light exposure, the BMDBM- centration to achieve the same effect when compared to commercial
NLCs had an increase in their UVA protection, whereas it declined for formulations. Despite their high-water resistance, these nanoparticles
the BMDBM-SLNs. All these findings illustrated that NLC-based sun could be eliminated using a towel or through exfoliation [157].
screens have tremendous photoprotective action, and they required a
lesser amount of the UV filter for this, hence significantly reducing the 4.13. Mesoporous silica nanoparticles
chances of UV-filter toxicity [92].
These are particles of mesoporous silica that have a honeycomb
4.12. Polymeric nanoparticles shape. The active compounds are loaded in a honeycomb shape. Meso
porous silica nanoparticles (MSNs) have numerous characteristics, and
Polymeric nanoparticles (PNs) are made up of natural or synthetic because of that, they are used extensively. These characteristics are their
polymers and have sizes of less than 1000 nm. Generally, biodegradable chemical stability, thermal stability, biocompatibility, ability to modify
polymers are utilized for their preparation so that the chances of accu their particle size, pore size, and morphology, easy synthesis, various
mulation and toxicity are insignificant. Poly(ε-caprolactone) and poly- techniques for surface functionalization of MSNs, high surface area, and
lactic acid, poly (glycolic-co-lactic acid) (PLGA), are the two most the possibility to manipulate their physicochemical properties [158,
commonly used biodegradable polymers [140–143]. These colloidal 159].
structures can transport both hydrophilic and lipophilic molecules, and In sunscreens, MSNs were initially utilized as protection devices
the nature of active molecules determines the choice of the polymer because TiO2 was coated with silica so that ROS generation was reduced.
(either hydrophilic or lipophilic) [143,144]. Some of the most popular However, instead of coating the MSNs, UV filters are incorporated into
methods for the preparation of PNs are spray drying [145], supercritical the MSN structure, which enhances the photoprotective effect. In
fluid [146], emulsion solvent evaporation [147], ionotropic gelation addition, various deleterious effects associated with UV filters, such as
[145], and nanoprecipitation [148]. PNs can be used as allergic reactions, cytotoxicity, and skin damage, are reduced [160,
prolonged-release reservoirs and as topical drug delivery systems due to 161].
their size, solubility, and stability, and all these factors are influenced by Knezevic et al. developed three mesoporous nanoparticles, periodic
their structure [91,149,150]. Polymeric nanoparticles are of two types, mesoporous organic nanoparticle with benzene (PMOBTB), periodic
nanospheres, and nanocapsules [151]. Nanocapsules have a polymeric mesoporous organic nanoparticle with ethane (PMOBTE), and MSNs, to
layer that encloses the oily or aqueous core, where the active molecule is determine their role in reducing the environmental and human health
either dissolved in the core or adsorbed to the polymeric coating. risks of sunscreen formulation. Initially, the photostability and UV
However, nanospheres have a matrix of polymers that either adsorb or protection of these particles were analyzed. After that, they were
entrap the active molecules. Overall, the nanocapsules have better analyzed for their potential to absorb avobenzone. Moreover, surface
loading capacity than the nanospheres and dissolve the lipophilic functionalization was performed for MSNs using either a combination of
compounds better due to the oily core [48,152,153]. Apart from this, Zn2+ and N-[3-(trimethoxysilyl)propyl]ethylenediamine (ZnDAMSN) or
due to their ability to modify its distribution, enhance the active mole N-[3-(trimethoxysilyl)propyl]ethylenediamine (DAMSN) alone. Zinc
cules’ adhesion to the skin, and enhance the water solubility of the ions aid in the repair of cutaneous tissue wounds, whereas N-[3-(tri
active molecules, they are comprehensively utilized as UV filter carriers methoxysilyl)propyl] ethylenediamine (DAMSN) functions as a
[154,155]. chelating ligand. The outcome showed that both PMOBTE and PMOBTB
Antioxidant properties are necessary for sunscreens apart from their had higher SPF values than MSNs. While the surface functionalization of
photoprotective properties so that the oxidative stress caused by sun MSNs significantly enhances the SPF, it was not as high as the SPF of the
exposure can be decreased. Polyphenols such as naringenin (a flavanone organic nanoparticles. To determine the effect of particle size on SPF
that is found in cocoa, oregano, tomato, grape, etc.) can be utilized in PMOBTB2, a smaller diameter size was developed. Compared to that of
combination with photoprotective ingredients. Naringenin significantly PMOBTB (larger diameter), the SPF of PMOBTB2 was significantly
reduces ROS and provides UV protection. However, naringenin has poor reduced. The PMOBTB2 diameter size was lower than that of MSNs, but
permeability and bioavailability, and these properties can be improved the SPF of PMOBTB2 was also significantly higher than that of MSNs.
by incorporating them into a nanosystem. Naringenin-loaded PLGA The presence of benzene bridges is assumed to be the reason for this, as
particles were developed by Joshi et al. to evaluate their antioxidant and they absorb UV radiation. Furthermore, the avobenzone absorption
UV protection properties [more details in table no: 3]. The results study indicated that the UV filter can be either incorporated into the
showed that compared to pure naringenin, naringenin-loaded PNs had mesopores or absorbed on the surface of mesopores. All the particles
higher SPF. PNs benefitted it in two ways: 1) their smaller size allowed were photostable and broad-spectrum UV filters with a critical wave
easy permeation, and 2) as they are lipophilic in nature, naringenin was length greater than 370 nm. Finally, it was recommended that
retentate in the epidermis for a longer duration that prevented its entry PMOBTB2 should be utilized for commercial sunscreen, even though
14
PMOBTE and PMOBTB had higher SPF because of the structural modi major advantages, the use of nanocrystals is associated with the
fications that can be made to PMOBTE2 [94]. solubility-enhancing property of various drugs [167]. Even though there
Octyl methoxycinnamate (OMC) is a type of organic UV filter that is are various available methods like the use of cosolvents, and complex
comprehensively utilized in sunscreen formulation due to its excellent ation with cyclodextrins, by which enhancement in the solubility can be
water resistance and UV-B absorption capabilities. However, OMC is obtained, out of these methods currently, the use of nanocrystals (nano
capable of penetrating deeper skin layers, causing systemic side effects, crystallization) is increasing day by day due to its higher drug loading
and in the presence of light, it degrades into products that have dele capacity as well as the use of completely biodegradable property con
terious effects on human health. Hence, Ambrogi et al. incorporated taining compounds like stabilizers ultimately gives completely safe
OMC into MCM-41 (Mobil Composition of Matter No.) pores using a products containing absolute pure drug materials in the final pro
solvent evaporation technique, with a UV-filter loading of 33 ± 1%. duct/formulations [96,168,169]. There are three well-known methods
After this, to delay the release, the pores of OMC-loaded MCM-41 were for the preparation of nanocrystals. a) Top-down method 2) Bottom-up
closed by coating TRI (tristearin), CER (ceresin), and STE (stearyl method 3) Combined method. In the top-down method, the name sug
alcohol) using the hot-melt technique. These coated OMC-loaded MCM- gests that the size reduction principle is being used in the preparation of
41 s were then loaded in an emulgel. In vitro release studies were per nanocrystals. Milling as well as homogenization under a high-pressure
formed using Franz cells for 8 h. Freshly prepared emulgel and emulgel principle is being applied in this method. In the bottom-up method,
stored for 30 days were used to determine the effect of storage on release the crystallization technique is applied. In the combined method, the
rates. Compared to the free formulation, the MCM-41 formulation principles of both previous methods are used for the production of
released a lower amount of UV filter, and the results also indicated that nanocrystals. Generally, in the pharmaceutical or cosmeceutical in
the storage did not affect the release profile. For the photostability dustries and in the production of sunscreen formulations, the top-down
studies, at 330 nm, the absorption spectra of the OMC-loaded MCM-41 method is preferred due to cost compliance as well as scale-up or pro
formulations were measured for 2 h using a spectrophotometer. The duction with much less effort. With varieties of research and advanced
results showed that no significant change was observed in the spectra; techniques in the year 2001, newly designed nanocrystals came into the
hence, the photostability was maintained. This study demonstrated that market with a size range under 100 nm by a combination of various
MSNs are potential nanoparticles that can be utilized in sunscreens to techniques. These newly developed nanocrystals are physically more
enhance the release duration and photostability of active molecules stable and easier to manufacture on a large scale. In 2006, patented
[162]. Daneluti et al. studied skin deposition and permeation of meso advanced nanocrystals/smart crystals were used widely in cosmeceut
porous silica SBA-15 incorporated with octyl methoxycinnamate (OMC), ical formulations as a solution to solubilization problems in conven
oxybenzone (OXY), avobenzone (AVO) sunscreen stick and compared it tional formulations [170]. As a result, the use of nanocrystals in the
to free UV filter containing stick. It was reported that for AVO and OXY, aqueous and nonaqueous phases in the formulations increased. It crosses
there was a significant reduction in their deposition in the stratum or penetrates the layers of the skin more efficiently, ultimately
corneum, viable epidermis, and dermis after application for 6h and 12 h. enhancing the concentration gradient in the skin due to enhancement in
However, for OMC there was no significant difference in skin deposition the surface area as well as dissolution [168].
due to its lipophilic nature. OXY-loaded SBA-15 stick had 30- and The efficacy of the various drugs along with nanocrystals has been
12-fold lower skin deposition after 6h and 12 h respectively compared to tested via various studies, which provide evidence/surety for their use in
the free UV filter-containing stick. Furthermore, in vitro SPF was sunscreen formulations. Juvena formulated rutin-containing nano
measured for the sample and it was reported that incorporation in crystal molecules that were more lipophilic in nature compared to their
SBA-15 resulted in a 94% increase in the SPF [163]. Daneluti et al. hydrophilic nature and most suitable for skin penetration, ultimately
further continued the experiments and determined the in vivo SPF and in giving very high bioactivity compared to molecules of hydrophilic na
vitro UVA-PF of this stick and compared the results with a free UV ture. A study conducted by Al Shaal et al. established the importance of
filter-containing stick and marketed stick available. The SPF of the free nanocrystal suspensions, as they enhance the properties of the drug,
UV filter stick was 50.4 ± 10.2 whereas this value was 63.7 ± 10.1 for such as the antioxidant effect of apigenin, compared to macro
the UV filter-loaded SBA-15 stick and 69.5 ± 14.4 for marketed free UV suspensions. Study data, which are given in Table 3, show that the
filter-containing sticks. Here, the SPF of the SBA-15 loaded stick was antioxidant effect of apigenin is enhanced with nanocrystal suspensions
only slightly lower than the marketed stick despite having a lower compared to macrosuspensions due to the higher surface area for free
content of UV filter compared to the marketed stick. Overall, it was radical reactions. Another study, which is mentioned in Table 3, shows
reported that SBA-15 enhanced the SPF by 26%. Interestingly, UVA-PF the advantages of cellulose nanocrystals derived from wood pulp.
for all the formulations was obtained lower than one-third of the SPF Environmental safety, patient compliance, toxicity, biodegradable na
which as per EU guidelines should be equal to or greater than one-third ture, waterproofing, and high photostability are all properties observed
of the SPF of the formulation [164]. Recently, Marcelino et al. developed in cellulose nanocrystals derived via an esterification process with cin
a sunscreen lipstick using TiO2 loaded into SBA-15. The formulation namoyl chloride. Zhang et al. discovered rod-shaped cinnamate-func
aimed at overcoming demerits of TiO2 such as aggregation and carrier tionalized cellulose nanocrystals that showed twice higher effects than
charge recombination. The result reported that 10% TiO2 incorporated sunscreen creams with an SPF of 50. Cellulose nanocrystals show an
into SBA-15 had greater SPF had photostability compared to the free excellent effect against UV rays due to the structure of the cinnamate
form of TiO2 and suggested that it can be used for developing group. Further data from the study are given in Table 3 [95]. After
broad-spectrum sunscreen, especially for sun protection of the lips observing all these data from various studies, one common conclusion is
[165]. that the use of cellulose nanocrystals, as well as normal nanocrystals
along with any drug molecule, enhances their performance with mini
4.14. Nanocrystals mum or sometimes without forming any adverse or side effects in the
sunscreen formulation compared to their absence. Liquid crystal based
Nanocrystals are nanoparticles used in sunscreen formulations; formulations should also be explored for better penetration [262,263].
generally, they are present in various sizes and shapes. Ideally, the size
range of these molecules is less than 1000 nm along with the presence of 4.15. Gelatin-based nanoparticles (GNPs)
a stabilizer for maintaining the stability of these molecules [166]. It
might be present in a spherical shape during an amorphous state or in a Gelatin contains excellent properties like biodegradability as well as
cuboidal shape during a crystalline state. Severe advantages are present it is also a safe polymer, a GRAS molecule as declared by U.S. FDA. GNPs
behind the use of nanocrystals in a sunscreen formulation. Out of these are nanoparticles that have mainly found their application in gene and
15
drug delivery systems however, their application in cosmetics is mini properly it can also have deleterious effects on the skin. They can
mally explored. GNPs have a special ability to provide their own anti remove in three ways: washing with water, cleanser, and cleanser oil. A
oxidant activity due to the presence of peptide sequence (His-Gly-Pro- study was carried out using non-water resistance and water resistance
Leu-Gly-Pro-Leu) in the structure of gelatin which prevents lipid per sunscreens in which the cleansing ability of all three was evaluated. The
oxidation. Camila Areias de Oliveira et al. utilized GNPs for incorpo participants were kept in a room with control temperature and humidity
rating rutin, a highly antioxidant compound, which would enhance the (20-24 ◦ C, 50%–60%) for 30 min after sunscreen application. In this,
effectiveness of sunscreen with synthetic UV-filter. It mainly focuses on photos were taken using VISIA Complexion Analysis System after sun
determining parameters such as the antioxidant and photoprotective screens application prior to washing and after washing. Under UV ra
effects of rutin-loaded gelatin-based nanoparticles (R-GNPs). In the diation, faces with sunscreen applied showed a specific dull red color,
study, authors had combined rutin-incorporated-GNPs loaded with this color was marked black using Adobe Photoshop CS6, and it indi
various organic UV filters like methoxydibenzoylmethane (BMDBM), cated the presence of sunscreen residue. The residue rate was calculated
ethylhexyl methoxycinnamate (EHMC), and ethylhexyl dimethyl PABA by taking the ratio of black pixels in a specific washing style photo to
(EHDP). Entrapment of rutin in gelatin-based nanoparticles was done black pixels in the positive control (photo of sunscreen applied on the
through a modified process in which the pH of the medium was kept whole face). For non-water resistance sunscreen, the residual rate for
alkaline as the solubility of rutin is a more alkaline medium which water, cleanser, and cleansing oil was found to be 54.0% ± 19.2%,
resulted in entrapment efficacy of 51. 8 ± 1.4% along with maintaining 15.6% ± 6.1%, and 13.4% ± 4.6%, respectively, whereas for water
the physical stability of rutin. Moreover, compared to the conventional resistance sunscreen, the residual rate for water, cleanser, and cleansing
use of rutin, the R-GNPs utilized a lesser amount of rutin because it could oil was found to be 59.3% ± 10.4%, 36.8% ± 8.8%, and 5.8% ± 3.3%,
form crosslinking with gelatin which directly increases entrapment ef respectively. Furthermore, the residual rate for the negative control
ficiency. The anti-oxidant assay reported that R-GNPs had enhanced the group for non-water resistance and water resistance sunscreen was 9.9%
antioxidant activity by 74% compared to free rutin because it main ± 4.8% and 3.2% ± 2.2%, respectively. The results demonstrate that
tained the free-radical scavenger property of rutin by preventing its non-water resistance sunscreen can be easily washed off by the cleanser
degradation. R-GNPs also enhanced the in-vitro SPF by 48% of the and cleansing oil, whereas for water resistance sunscreen, cleansing oil
emulsion containing a mixture of R-GNPs with the organic filters [171]. is the optimum cleansing option [180].
In another study, water resistance of different sunscreens was studied
5. Patents with nanotechnology-based sunscreen at different water temperature (20 ◦ C, 25 ◦ C and 30 ◦ C). Results suggest
that three products were not affected by the temperature however, one
As shown in the above section, various nanoparticles are utilized for product washed off at high temperature [181]. Furthermore, the color or
developing sun protection formulations. Some of these nanoparticle- appearance after application of sunscreen is equally important. The
based formulations have been patented over the past year. Some of inorganic filters (zinc oxide and titanium dioxide) deposit in the skin and
these patents are shown in Table 4. provide whitish appearance to skin, which is not acceptable by the
consumers [182].
6. Critical sunscreen factors
6.2. Skin phototypes
6.1. Sunscreen vehicle, application, and removal
There are numerous methods for the characterization of skin
Worldwide sunscreens are available in various forms such as gels, pigmentation and identifying different skin phototypes (SPT), but indi
lotion, and creams. All these are emulsion-based products and such vidual typology angle (ITA) and Fitzpatrick phototype classification are
vehicles affect their uptake and efficacy. Generally, two emulsion types the two most widely used methods. From this, ITA is the more precise
are used most widely either water in oil (W/O) or oil in water (O/W) one but it requires colorimetry measurement (detailed classification is
[172]. In one of the in vitro studies, sunscreen with the same UV filter given in Table 5) [183–185]. All the SPT have different sun protection
and different vehicles such as clear lipo-alcoholic spray, O/W spray, gel, requirements. For instance, compared to the dark-skin population, the
O/W cream, and W/O cream was evaluated for its efficacy. The results light-skin population has a lower eumelanin/pheomelanin ratio and a
showed that contact with water led to a reduction in efficacy for an O/W lower amount of melanin in the upper layer of the epidermis. Therefore,
emulsion whereas, despite the water contact, the efficacy of W/O UVB exposure leads to DNA damage in both the upper epidermis layer
emulsion was not diminished due to the presence of a water-insoluble and the basal layer, whereas this damage is limited to the upper
emulsifier and a low hydrophilic-lipophilic balance (HLB) value. Addi epidermis layer in the dark skin population. Additionally, DNA repair is
tionally, W/O emulsion had the highest SPF out of all the formulations also efficient in the dark skin population [186]. So, the light skin pop
evaluated. However, one major advantage of W/O formulation is its ulation is more prone to damage caused by UVB. On contrary to that, the
non-comedogenic properties [173–175]. Overall, for optimum sun dark skin population is more prone to hyperpigmentation caused by
protection, it is beneficial to use a W/O type of formulation. But, some UVA and visible light [187–189]. Therefore, for the light skin population
types of O/W of the formulation are preferred by the patients due to sunscreen which provides optimum UVB protection is more beneficial
their non-comedogenic properties and lighter feel. and for the dark skin, population sunscreen with optimum UVA and
U.S. FDA has recommended applying 2 mg/cm2 of sunscreen for visible light protection is more beneficial. For the dark skin population,
obtaining desired sun protection. However, numerous studies have pigmentary titanium dioxide and/or iron oxides containing tinted sun
confirmed that there is underapplication of sunscreen and only 25-50% screen with a color similar to their complexion are more useful [190]. In
of the recommended is applied [176–178]. For compensating this it is general, for the light skin population, an SPF of 50+ is recommended,
recommended that a broad-spectrum sunscreen with an SPF of 30 or and for the dark skin population, an SPF of 30+ is recommended [191].
higher should be used [175].
As per guidelines suggested by the American Academy of Derma 6.3. Age-related factors
tology Association apply sunscreen at least 15 min before going outdoor.
It requires around 15 min to absorb inside the skin and provide pro Amongst many factors, UV radiation is one of the causative agents of
tection. Moreover, it has been suggested that re-apply sunscreen after skin aging. Recurrent contact with UV rays destroys collagen and change
every 2 h. Reapplication is required after sweating and swimming also the generation of new collagen due to modifications in elastin fibres
[179]. [192]. Due to the absence of elastin and collagen the repair property of
Sunscreen helps in preventing damage to the skin, but if not removed skin loses, the strength & flexibility of skin also loses. Protection
16
Table 4
Patents with nanotechnology-based sun protection formulation.
Patent No. Title Current Assignee Brief description
AU2021104084A4 (Status: Lignin-based nano-film with antibacterial Qilu University of The patent AU2021104084A4 presents a patent for a lignin-based nano-film
Active) and sunscreen property and preparation Technology, that possesses sunscreen and antibacterial properties, along with a detailed
method thereof Taishan University method for its preparation. The nano-film is fabricated using lignin, a key
component derived from biomass, which undergoes a self-crosslinking
reaction facilitated by a crosslinking agent. To enhance its functionality, the
lignin is combined with an antibacterial agent, resulting in a self-
polymerizing polymer suitable for forming a film through a spray-coating
process.
The preparation method consists of three main steps: (1) dissolving lignin in
a solvent, (2) cross-linking the lignin with a cross-linking agent to achieve
self-polymerization, and (3) compounding the self-polymerizing lignin with
an antibacterial agent.
Compared to existing technologies, the resulting nano-film exhibits
remarkable properties such as effective ultraviolet absorption and
antibacterial activity, while maintaining stability. The unique property of
the patent is its utilization of lignin, a natural and biodegradable material,
as the matrix for the nano-film which promotes sustainable use of lignin.
Additionally, the film do not produced harmful residues during its
utilization. Overall, this patent offers a straightforward and efficient
approach to creating a lignin-based nano-film with desirable attributes
suitable for various applications.
US10596079B2 (Status: High efficiency sunscreen composition Deckner Consulting The patent US10596079B2 presents oil-in-water dispersions and sunscreen
Active) Services LLC compositions that demonstrate a high level of efficacy in terms of sun
protection factor (SPF) when applied in vivo. These compositions possess the
unique ability to both absorb and scatter ultraviolet (UV) light. They consist
of discrete oil particles that are enclosed within a solid coating, dispersed
within an aqueous phase. Each of these oil particles contains an organic
compound capable of absorbing either ultraviolet A (UVA) or ultraviolet B
(UVB) radiation, or even both, along with an optional addition of a
photostabilizer. This particular combination of ingredients contributes
significantly to the improved performance of the sunscreen composition,
enabling effective protection against the harmful effects of the sun’s rays.
US7108860B2 (Status: Sunscreen compositions Egdewell Personal The patent US7108860B2 aims to develop a cosmetic composition that can
Active) Care Brands LLC, be applied effectively as a lotion, cream, or gel. The invention sets forth
Sun Pharmaceuticals specific objectives for this composition. Firstly, it should maintain a
Corp, consistent viscosity across a wide range of temperatures, ensuring stability.
Playtex Products LLC Additionally, the composition should be dispensed smoothly from the
dispenser without dripping or running, even at higher temperatures. This
prevents wastage and ensures precise application. Furthermore, upon
application to the skin at elevated temperatures, the composition should
remain in place without dripping or running, offering a clean experience.
The desired texture of the composition is soft and silky, allowing for even
spreading over the skin. Moreover, the composition should function as a
sunscreen, providing protection against harmful UV radiation. Specifically
for the sunscreen formulation, it should be formulated as a stable oil-in-
water emulsion or gel, ensuring durability and effectiveness. Additionally,
SUNSPHERE® were also utilized as SPF booster.
CN115154365A (Status: Non-permeation sunscreen nano particle Jiangnan University The patent CN115154365A introduces a novel non-permeable sunscreen
Pending) and application thereof nanoparticle and its utilization for developing sun protecting formulation.
The method involves dispersing wax particles in water and subsequently
incorporating dopamine, dopamine methacrylamide, and methoxysilane
into the mixture. After the reaction, the resulting product undergoes
heating, wax removal, and subsequent washing and drying processes to
obtain non-permeable sunscreen nanoparticles with a distinctive two-
dimensional sheet structure.
These sunscreen nanoparticles, derived from natural sources, possess a
unique property that prevents them from penetrating the skin due to their
two-dimensional sheet structure. Furthermore, they have been determined
to be safe, non-toxic, and have effectiveness in shielding against harmful
ultraviolet radiation. The patent emphasizes the potential application of
these nanoparticles in various daily chemical products, particularly in the
field of sun protection.
CN102697663B (Status: Composite sun-screening agent nano- Southeast University The CN102697663B patent introduces a unique nano-structure lipid carrier,
Expired-fee related)> structure lipid carrier and preparation designed specifically for a composite sun-screening agent. This carrier is
method thereof loaded with two active ingredients, namely
diethylaminohydroxylbenzoylhexyl benzoate and ethylhexyl triazone. The
distinctive feature of the nano-structure lipid carrier lies in its composition,
which includes ethylhexyl triazone (1-10% by weight),
diethylaminohydroxylbenzoylhexyl benzoate (2-20% by weight), an
emulsifying agent (3-15% by weight), a composite lipid material (10-15%
by weight), and deionized water to balance the mixture. The composite lipid
material is a blend of solid and liquid lipids, chosen from various
compounds like caprylic capric triglyceride, acetylated monoglyceride,
glycerin monostearate, grape seed oil, and glyceride L.
17
Patent No. Title Current Assignee Brief description
One notable advantage of this nano-structure lipid carrier is its high

stability, ensuring the longevity and efficacy of the active ingredients.
Additionally, the patent describes a straightforward and controlled
preparation method for the carrier, which yields consistent results and can
be employed in the development of cosmetics containing ethylhexyl
triazone and diethylaminohydroxylbenzoylhexyl benzoate.
KR20180024903A (Status: Stably-suspended polymer composite – KR20180024903A presents a novel polymeric nanocomposite particle and
Application discontinued) nanoparticles containing organic its production method. The particle contains organic ultraviolet (UV)
sunscreen agents and preparing method blocking agent that is stabilized by the particle. The invention offers the
thereof following main advantages:
1. Improved Particle Dispersion: The polymeric nanocomposite particles
greatly enhance the stability of particle dispersion. This ensures that when
they are incorporated into cosmetic formulations, small-sized particles
(ranging from 10 to 10,000 nm) are uniformly dispersed, leading to better
usability.
2. Enhanced UV Blocking: By maintaining the UV blocking components (UV
blocking agent) in an amorphous state rather than a crystalline state, the
invention significantly boosts the effectiveness of UV protection. This results
in better shielding against harmful UV radiation.
3. Prevention of Skin Irritation: The polymeric nanocomposite particles are
enveloped within a polymer. This encapsulation serves as a barrier,
preventing direct contact of the UV blocking agent with the skin. As a result,
the potential for skin irritation is minimized when the particles are applied
topically.
US20100003204A1 (Status: Nanoparticle hybrid sunscreens Energy Materials Corp The patent application US20100003204A1 presents a novel chemical
Abandoned) composition that possesses desirable sunscreen properties. This composition
consists of spherical particles with diameters ranging from 200 nm to 10 μm.
The particles are synthesized through emulsion polymerization of
tetraalkoxysilanes, organotrialkoxysilanes, or organobridged
trialkoxysilanes with a dye monomer. The dye monomer has multiple
alkoxysilyl groups attached to a bridging chromophore.
These spherical particles have the ability to absorb ultraviolet (UV) light.
The chosen dye can be any organic chromophore that can accommodate
multiple trialkoxysilyl groups, ensuring strong covalent attachment to the
spheres and preventing dye leakage. The emulsion polymerization process,
utilizing formic acid, toluene, and the monomer, enables large-scale
synthesis (over 100 g) of uniform particles under acidic, non-aqueous
conditions, eliminating the need for surfactants.
The particles, especially those smaller than 1 μm in diameter, have a smooth
texture comparable to talc. This property makes them suitable for
formulating sunscreen creams or lotions that provide a smooth and pleasant
application experience.
EP1468672B1 (Status: Not- Sunscreen oil-water nanoemulsion, its L’Oréal SA The patent EP1468672B1 introduces an oil-in-water photoprotective
in-force) method of preparation and its uses in emulsion that contains tiny oil globules with an average diameter of 500 nm
cosmetics and dermatology or less. This emulsion incorporates both ionic polymer particles and a
filtering system to offer protection against UV radiation.
What sets this filtering system apart is the inclusion of at least one UV-A
filter from the 4,4-diarylbutadiene category. This specific type of UV-A filter
plays a crucial role in safeguarding the skin from the harmful effects of UV
radiation. Moreover, this emulsion are free from surfactant therefore, skin
irritation occurring sensitive skin due to surfactant is prevented.
methods against UV rays helps the prevention of skin aging such as

Table 5
sunglasses, covering from cloth, and use of sunscreen. Nowadays
Classification of skin phototypes.
healthcare practitioners highly recommend use of sunscreen in every
Fitzpatrick Skin color (ITA Individual Description age [193]. The use of sunscreen protects skin from harmful UV radia
phototype classification) Typology Angle
tion, avoid tanning, sunburns, face blotchiness, premature aging, and
(ITA)
decreases the occurrence of skin cancer. As per guidelines provided by
I Very light ITA◦ > 55◦ Never tans, always
the American Academy of Dermatology in all age including kids need to
burns
II Light 41◦ < ITA◦ < 55◦ Sometimes tans, burns
utilize sunscreen with an SPF of 30 or above [194]. As per age SPF has
easily been mentioned, babies upto 6months (no need of sunscreen, covering is
III Intermediate 28◦ < ITA◦ < 41◦ Always tans, burns required), 6 months to 6 years (100% mineral sunscreen SPF 50), 6–16
sometimes years (SPF 50), 16-25 years (SPF 50), 25–35 years (100% mineral matte
IV Tan 10◦ < ITA◦ < 28◦ Easily tans, burns
sunscreen SPF 40, antioxidant-infused sunscreen with vitamin C SPF
rarely
V Brown − 30◦ < ITA◦ < Moderately 50), 35–45 years (100% mineral lotion SPF 50), 45–60 years (SPF 40 or
10◦ pigmented, easily 50), 60+ years (SPF 40-50).
tans, burns rarely
VI Dark ITA◦ > − 30◦ Highly pigmented,
intensely tans, burns
rarely
6.4. Long-term effects of sunscreen
Sunscreen has been proven effective in prevention of several diseases

such as skin cancer and melanoma. However, application of sunscreens
18
for longer time can induce several skin conditions such as dermatitis, their nature. The in vivo evaluation involves the selection of human
lichens planus, and allergy. It has been reported that long term usage of volunteers, product application on the skin, and measurement of UVA or
UV filters in barrier sunscreen can trigger lichens planus condition UVB protection by determining the time required to induce sunburn or
[195]. Moreover, patients with sensitive skin and eczema also showed pigmentation using an artificial UV source. Alternative to the in vivo
symptoms of irritant contact dermatitis after application of sunscreen. methods are the in vitro methods in which the UVA or UVB protection is
Furthermore, some people can be allergic to particular ingredient of measured using a device called a spectrophotometer. To date, various in
sunscreen (preservative, fragrance) and can get allergic contact vitro methods have been discovered and standardized [199,200].
dermatitis resulting rashes, blisters, and itchy skin. Photo contact Although the in vitro methods are comparatively time efficient and
dermatitis is very rare condition which can occur in some person due to cheaper than the in vivo methods, they are not employed for SPF testing
reaction between a sunscreen ingredient and UV light that leads to skin because they lack equivalence to the in vivo methods. Hence, they are
reaction [196]. not included by the regulatory body. For the sunscreens, three tests are
performed, mainly SPF, UV protection, and water resistance. Further
6.5. Price of sunscreen products more, information is given in Table 6. Apart from these mainstream
tests, some of the ex vivo testing are also preferred for determining the
The price of sunscreen products is another major factor that directly efficacy and stability of the sunscreen during research work a brief
makes a huge impact on use by consumers. With the enhancement in description of these tests is mentioned in Table 7.
awareness regarding the importance of sunscreen formulation; nowa
days, the use of these products has increased. Here, we have collected 8. Sunscreen with additional properties (combination sunscreen
data from different research studies which have been conducted to note formulation)
down the effects of price and to study how much money can consumers
afford to spend on sunscreen, which directly affects the market cap. One 8.1. Sunscreen against blue light
study gives data collection on the price of sunscreen formulations which
is as per the weight of the sunscreen and from protection factor (SPF Blue light radiation has a wavelength ranging from 380 nm to 500
value). As per the literature, a total of 607 sunscreen products were nm. This radiation is generally released by the sun and electronic devices
collected which were further divided into various subtypes based on such as laptops, computers, tablets, and smartphones. This radiation is
different parameters. As per the data, sunscreen prices were taken as used in combination with photosynthesizing drugs for the treatment of
price (in U.S. Dollars ($)) per 10 g. Under protection factors, sunscreens cancer. However, they can penetrate deeper skin layers and cause
were classified into three categories as per the labelling condition of SPF detrimental effects, such as weakening of the epidermal barrier and
value. Sunscreen with SPF values around 15, between 15 and 30, and production of ROS, which leads to accelerated aging and extracellular
between 30 and 59.9 were respectively categorized as medium protec matrix damage. Thus, skin protection against blue light becomes
tion (MP), high protection (HP), and very high protection (VHP). Out of essential. Studies have suggested that UV filters can also block blue light
607 sunscreens, 170 sunscreens belong to the category of MP with a radiation apart from their ability to block UV radiation. “City Skin Age
median price range of 1.7 US$ per 10 g with a ranging price value be Defense (SPF 50 and PA+++)” developed by Murad and “Sun Expertise
tween 0.1 and 20.2, 279 sunscreens belong to the category of HP with a (SPF 50+)” developed by SKEYDOR are two examples of recent sun
median price range of 1.5 US$ per 10 g with ranging price value between screens that can protect skin against blue light [224–228]. Exosome
0.1 and 20.2, 158 sunscreens belong to the category of VHP with the based formulations are also very sucessful for the cancer in the recent
median price range of 2.0 US$ per 10 g with ranging price value between past and scientist are also exploring the same for the sunscreen appli
0.4 and 9.8. Apart from this, sunscreens were also classified according to cation [260,261].
their weight (in grams) into three subtypes: a weight between 30 and 99,
100 to 199, and above 200. Out of 607 sunscreens, 229 sunscreens were 8.2. Sunscreen against environmental pollutants
having weight range between 30 and 99 with a median price range of 3.7
US$ per 10 g with a ranging price value between 0.9 and 44.8, 238 Air is composed of various pollutants, such as nitrogen oxides (NOx),
sunscreens had a weight range between 100 and 199 with a median sulfur oxides (SO2), polyaromatic hydrocarbons, and particulate matter
price range of 1.5 US$ per 10 g with ranging price value between 0.4 and (PM), that have detrimental effects on the skin. These pollutants can
4.2, and 139 sunscreens weighted 200 with a median price range of 1.0 cause wrinkle formation, aggravation of acne, uneven skin tone, loss of
US$ per 10 g with ranging price value between 0.1 and 6.4. In the firmness, dark spots, and skin dryness by inducing hyperpigmentation,
literature authors rightly show observation data on budget related to the inflammation, and collagen breakdown. To decrease these effects, an
price of sunscreen as per the week as well as for a year depending on tioxidants are added to the sunscreen. They act through various mech
certain factors, like gender and age, that directly give an idea about the anisms, such as promoting elastin/collagen synthesis and exfoliating or
quantity of sunscreen utilize as per the body surface area, which varies cleaning the skin so that the particle load decreases and reduces
from person to person. Finally, it was concluded that photo-sensitive inflammation. Some of the commercially available sunscreens with anti-
people should prefer purchasing sunscreen bottles with large volumes pollutant effects are “Clarins UV plus antipollution SPF 50 Broad Spec
as they are a cost-effective solution; in addition to that, people should trum SPF 50” with white tea extract and “Dr. Dennis Cross Dot Sot Sun
utilize sun-protective clothes to reduce sunscreen expenditures [197]. In Defense” with the melatonin defense complex [229].
another study, data were collected regarding the prices of highly rated
sunscreens on amazon.com. These sunscreens were divided into two 8.3. Sunscreen combined with DNA repair enzymes
categories: high-price sunscreens and low-price sunscreens. The results
demonstrate that there was a 3000% variation in the prices of low and Sun rays can penetrate the deeper skin cells that are prone to cancer.
high-cost sunscreen. Additionally, it was reported that maximum sun The early-stage symptoms of the damage are in the form of wrinkle
screens were not following the AAD (American academy of derma formation, hyperpigmentation, and texture and tone loss. In the long
tology) guideline, which states that the sunscreen should have at least 30 term, this leads to cancer if the DNA damage is not repaired. In contrast,
SPF, broad spectrum, and sweat and water resistance [198]. the protection provided by traditional sunscreen is passive, due to which
the damage cannot be cured. Hence, a newer approach should be
7. Testing methods for sunscreen efficacy developed that has active protection against these damages. This can be
achieved by using DNA repair enzyme-loaded liposomes and antioxi
The efficacy of sunscreens is evaluated on human subjects because of dants [230–232].
19
Table 6 Table 6 (continued )

Sunscreen testing methods along with their types. Sunscreens Sub-types Description Reference
Sunscreens Sub-types Description Reference evaluation of methods
evaluation of methods methods
methods
UVA-PF/SPFin-vivo ratio.
SPF Testing In-vivo • "Gold standard" Method & [201,202] • Criteria for a broad-spectrum
methods testing Only approved methods by the sunscreen
regulatory bodies. 1. ISO––CW ≥ 370 nm and
• The formula for the UVA-PF/SPFin-vivo ratio ≥1/3.
MEDp 2. U.S.FDA = CW ≥ 370 nm.
calculation of SPFi =
MEDu Water resistance In-vivo • Available guidelines [212,
• Available guidelines test— testing 1. U.S.FDA 2021 215–217]
1. U.S.FDA 2021 For optional 2. COLIPA 2005
2. ISO 24444:2019 label claim of 3. ISO 16217:2020 = for water
3. CEN 2006 water resistance immersion.
In-vitro • Currently, no method is not [203] 4. ISO 18861:2020 = for
testing available with accurate and evaluating water resistance.
precise results. In-vitro • Currently, in-vitro water [218,219]
• Accuracy and reproducible testing resistance test methods are not
results depend on 2 factors available.
1. Product application • Two tried methods (not
2. Testing vehicle/substrate as succeed)
a skin surrogate. 1. plate method.
Hybrid • Two methods [204–206] 2. solution method.
testing • 1. HDRS = the combination
of in-vitro transmittance SPFi = Sun protection factor of an individual; MED = Minimal Erythemal Dose; U.S.
measurement and non- FDA = United States Food and Drug Administration; ISO = International Organi
erythemal in-vivo testing. zation for Standardization; CEN = European Committee for Standardisation; HDRS
• 2. PDRS = the combination of = Hybrid diffuse reflectance spectroscopy; PDRS = Polychromatic diffuse reflectance
in-vitro transmittance spectroscopy; U.S.FDA IPD = Immediate pigment darkening; PPD = Persistent
measurement and sub- pigment darkening; MPD = Minimum pigmentation dose; COLIPA = European
erythemal in-vivo testing.
Cosmetic and Perfumery Association.
• No guidelines are available
right now.
ISO/CD 23698 - is currently The utilization of DNA repair enzymes in sunscreens aids in DNA
under development repairs. The immune system can be strengthened against the tumor, and
In-silico • Computational simulation [207–209]
the mutation rates can be reduced by the use of DNA repair enzymes,
testing approaches that utilize UV
spectra of sunscreen such as endogenous repair enzymes, to directly repair the DNA. Some of
ingredients to predict the SPF the widely utilized DNA repair enzymes in sunscreens are 8-oxoguaine
value without the involvement glycosylase, photolyase, T4 endonuclease, and the combination of
of humans in the trials.
photolyase and T4 endonuclease. All these enzymes can prevent ma
• Two free simulation tools are
available for calculating
lignancies. 8-Oxoguanine glycosylase is a plant-derived enzyme ob
absorbance for SPF tained from Arabidopsis thaliana, while photolyase is derived from a
1. “Sunscreen optimizer” from cyanobacteria species called Aspergillus nidulans. The T4 endonuclease
DSM (T4N5) enzyme is obtained from Micrococcus luteus, a microbial species
2. “Sunscreen simulator” from
that have UV-resistance properties. The combination of photolyase and
BASF
• calculate UVA-PF/SPF ratio, T4N5 was added to conventional sunscreen and has been widely eval
and the critical wavelength uated for its effects. Carducci et al. demonstrated that compared to
(CW) conventional sunscreen, combination-loaded sunscreen significantly
UVA Protection In-vivo • Available guidelines [209–211]
decreased field cancerization and UV-induced cyclobutane pyrimidine
Testing methods testing 1. U.S.FDA 2007
2. ISO 24442:2022
dimers (CPDs) in 28 patients. On the other hand, another study indicated
3. CEN 2006 that the combination successfully prevented aging by reducing hyper
• UVA protection factor expression of the c-FOS gene and telomere shortening. All this indicates
measurement approaches. the beneficial effects of the concurrent utilization of DNA repair en
1- IPD = The ratio of the
zymes in the sunscreen formulation [230,231,233,234].
amount of UVA required to
produce IPD on protected skin
and unprotected skin. 8.4. Sunscreen against thermal IR
2- PPD = The ratio of the UVA
dose required to produce MPD
when the skin is protected with Sunscreens mainly focus on preventing the damage caused by UVA
sunscreen to the dose required and UVB radiation, but the effect of infrared radiation is not considered.
when the skin is unprotected. They account for 54.3% of sun rays and can enhance the activity of
2(a)- Formula: PPD − PF =
MMP-1 and MMP-9 in addition to the production of ROS radicals. All
MEDp
MPDU this causes damage to the collagen content of the skin. Hence, it is clear
In-vitro • Available guidelines [212–214] that sunscreens should contain agents such as antioxidants to reverse the
testing 1. U.S.FDA 2021 action of IR radiation. A study conducted by Kim et al. through in vivo
2. ISO 24443:2021
methods evaluated the IR protection of sunscreen using a reflectance-
3. COLIPA 2007
• Increasingly recognized by determining probe and a benchtop model-based IR source in 155
numerous authorities UVA Korean volunteers. The results confirmed that sunscreen was successful
Protection performance is in providing better IPF (infrared protection factor) than unprotected
calculated by either CW or skin, and in addition, the correlation between inorganic filters and IPF
was also demonstrated. It is also reported that chronic exposure to IR
20
Table 7 9. Safety and regulatory aspects of sunscreen formulations

Various ex vivo methods for evaluating the stability and efficacy of sunscreen.
Ex vivo methods Description Reference Similar to other conventional formulations in sunscreen products,
safety, as well as regulatory aspects, is essential for the maintenance of
Radical skin protection factor • The principle of RSF is based on [220]
(RSF) the determination of the number of proper quality and excellent efficacy with less/no toxic effects, which
free radicals generated on protected opens doors in the direction of safer use along with patient compliance.
skin to unprotected skin through Along with the tremendously positive effects of various available sun
electron spin spectroscopy (ESR). screen creams on skin protection, many skin-related problems, such as
• The number of free radicals
produced is measured through their
dermatitis by various photoallergic reactions, fluctuation in the level of
reaction with nitroxyl substrate vitamin D, and estrogenicity, have been noted to be associated with
2,2,5,5 tetramethylpyrrolidine-N- different ingredients used in sunscreen formulations [240,241], which
oxyl PCA which is a probe for ultimately produces harmful effects on long-term use. Due to all these
detection through ESR.
reasons and to improve quality as well as to control the harmful effects,
TBARS assay (Thiobarbituric • It is an assay used to determine [221,
acid reactive species) both direct activity sunscreen to 222] regulation is required. Various regulatory agencies have made their
prevent ROS generation and their guidelines as well as laws to overcome these problems.
photostability. Sunscreen formulations are given without any type of prescription in
• The assay is based on the principle many countries as “OTC” drugs; therefore, many times due to a lack of
of reaction between
malondialdehyde (a predominant
sufficient knowledge and misleading information, incomplete informa
secondary product of lipid tion in the labelling of sunscreen formulations leads to various types of
peroxidation) and TBA to form an serious toxic effects. On the other hand, in the USA, all these types of
adduct of MDA-TBA2 that produced formulations, including sunscreen products, are given only on proper
red-pink color. The absorbance of
prescriptions and regulated by the U.S.FDA, which ultimately solves all
this product is measured at 532 nm
and compared with the standard these problems of skin toxicity due to overuse. The overuse of highly
calibration curve of MDA. specific pathogen-free (SPF)-containing formulations may lead to life-
HPLC-TBARS-EVSC assay • A newer approach focused on [223] threatening diseases such as melanoma, as established in a study con
(High-Pressure Liquid measuring lipid peroxidation value ducted by Gorham et al. [242,243]. The use of various organic sub
Chromatography- on an ex vivo stratum corneum
stances, such as oxybenzone and PABA, also shows photoallergic
Thiobarbituric acid reactive obtained through tape stripping.
species-ex vivo stratum • The major advantage of HPLC- reactions [244]. The evaluation of nanoparticle-based sunscreen for
corneum) TBARS-EVSC is that it utilizes HPLC mulations is ongoing because the proper pathway for the penetration of
for the detection of the amount of molecules such as TiO2 has not been determined [245,246] while
MDA, which provides more accurate
various contraindicated study data show fluctuations in the level of
results of efficacy and safety of
sunscreen formed on the skin that vitamin D and its synthesis after the use of sunscreen formulations in
was removed non-invasive through patients [247,248]. In the recent era, with the vast use of advanced
tape stripping after UV irradiation nanoparticles/materials containing sunscreens, the Organization for
whereas TBARS utilizes colorimetry Economic Co-operation and Development made a “Sponsorship Program
or fluorimetry for detection of MDA
for the Testing of Manufactured Nanomaterials” in 2007 with the pur
formed on skin that is removed
before and then irradiated with a UV pose of enhancing the testing of various nanomaterials containing
source. nanoparticles under the size of 100 nm in their structure to overcome
toxicity problems. Sunscreens containing smaller nanoparticles are more
dangerous than those containing larger nanoparticles [169,249].
radiation can cause aging. To prevent this, various sunscreens with IR In different countries, with their regulatory guidelines on nano
protection have been introduced to the market in recent times. For particle use and labeling, conditions vary from each other. U.S.FDA has
instance, Skin Medica has a product called “Total defense and repair SPF not defined nanoparticles as appropriate for sunscreen use like the other
34”, which contains an antioxidant complex that reduces the fine line regulatory agencies [250]. In 2014, the Sunscreen Innovation Act was
and wrinkles [235–237]. established, which ultimately gives surety regarding their use for the
people of the USA after gaining the proper data of their safety studies as
8.5. Sunscreen with antioxidants and anti-aging well as verifying the properties of UV filter efficacy and toxicity data
from the manufacturers. [251,252]. As per the rules and regulations, the
Conventional sunscreens utilize organic and inorganic filters that criteria of the U.S.FDA claim of the broad spectrum can be given only
have many undesirable effects. These effects can be reduced by after passing the criteria of critical wavelength (370 nm). In the USA, for
decreasing the use of these filters, which can be achieved by using the calculations of protection factors, testing data of UVA and UVB is a
natural ingredients. The natural ingredients also provide antioxidant mandatory requirement. In European countries, all safety and regulation
and anti-aging properties, apart from their UV protection. A patented, perspectives are being regulated by SCCNFP (Scientific Committee on
with US patent No. 8,337,820b2, water-soluble sunscreen was devel Cosmetic and Non-Food Products intended for Consumers). For the
oped to prevent UV damage to various sensitive skin types, such as proper safety establishment of sunscreen formulations, the EU has set
people with rosacea. It includes N-acetyl-tyrosine, histidine, 5-hydroxy- passing criteria with an SPF/UVA-PF ratio of ≤3 along with a critical
tryptophan extracted from Griffonia simplicifolia, and TiO2. The absence wavelength of greater than 370 nm [253,254]. The EU has made very
of organic molecules prevented flushing, erythema, and inflammation. strict regulations and criteria for sunscreen products considering high
Apart from this, a sunscreen with tomato lycopene (antioxidant) had an safety with minimum/no toxicity level from the patient compliance
SPF of 20 and provided antiaging effects by preventing fine lines and perspective. As per the EU, sunscreen formulations with a minimum of 6
wrinkles. One other sunscreen developed by Blossom Kochhar Aroma SPF values and with the proper in vitro SPF/UVA testing method are
Magic added cucumber extract as an antioxidant, as it has numerous
given approval for manufacturing as well as for sale with the proper
benefits, such as enhanced UV protection, skin friendliness, anti-aging, labelling conditions with all necessary instructions for the safer use of
nongreasy, and the presence of various vitamins [103,238,239].
patients [251,255].
On the other hand, in countries such as Australia with the
enhancement of skin cancer cases in a couple of years, Therapeutic
21
Goods Administration (TGA), the regulatory authority responsible for 11. Future landscapes and conclusion
the approval of various sunscreen formulations, became strict in the
direction of patient safety. In Australia, these sunscreens are classified as The number of UV-induced skin disorder patients is increasing
therapeutic goods or cosmetic sunscreens. Cosmetic sunscreens are continuously; hence, sunscreen application is crucial to prevent/reduce
something known as secondary sunscreens, as they never contain skin such cases. The advanced nanotechnology-based sunscreen has multi
protection and act as the main labelling requirement. Secondary sun fold benefits compared to the conventional formulation. However, there
screen formulations contain skin-protecting agents and moisturizing is some issue with their safety, especially related to their toxicity.
agents up to the SPF level of 15, while primary sunscreen formulations Studies have shown the toxic effects of some of the nanosunscreens, and
contain an SPF value of greater than 15 for protection against UV rays regulatory authorities all over the globe have established special regu
[256]. As per TGA in sunscreen formulations labelling the particle size is lations for such nanosystem-based sunscreens. Apart from this, the
not mandatory with the use of various nanosize components such as testing methods’ for sunscreen are continuously evolving. In vitro testing
titanium dioxide and zinc oxide. A wavelength of 280–320 nm with a methods for some of the tests have already been developed, whereas for
passage percentage of less than 10% can be considered UVA protection other methods, in vivo testing is still developing. Moreover, combina
as per the regulatory authority of Australia. In African countries such as tional sunscreens are increasingly being developed and sunscreens are
South Africa, compliance with photostability testing of UVA as well as continuously evolving through the addition of features that enhance
with ISO 24443 is a necessary requirement for the approval of sunscreen beauty, for instance, tinted sunscreens are getting more popular day by
formulations [255]. day because they provide an even tone to the skin. Apart from this,
natural ingredient utilization in sunscreen is also enhancing day-by-day
10. Challenges due to its multiple benefits. In the future, one common regulatory
guideline should be prepared that includes all the necessary parameters
In this article, previous effects of UV rays on the skin, solutions, and of sunscreen, such as its testing, usage frequency, and labeling re
regulations have been discussed very well. Numerous hurdles are quirements, so that all the doubts for consumers as well as for the
encountered by people while applying sunscreen Generally, Obstacles manufacturer are resolved and there is a better utilization of the sun
come from both sides, from the manufacturer as well as from the con screen. This will also bring the manufacturing cost lower, which will
sumer side during use. From the manufacturer’s side during the testing make sunscreens more affordable. Furthermore, awareness regarding
of sunscreen formulations to check the effectiveness as well as toxicity the correct interpretation of labeling and usage of sunscreen should be
and for the labeling requirements as per the guidelines of respective spread among the customer by the regulatory agencies. Overall,
regulatory authorities. During testing on human subjects, a major nanosystem-based sunscreens are highly beneficial, but more research
challenge comes due to the highly carcinogenic effect of UV exposure, regarding their safety, stability, and efficacy should be conducted. All of
and for the purpose of gaining proper study data, ethical challenges this will tremendously improve nanosystem-based sunscreen utilization
come ahead of the manufacturer. Apart from this, other challenges, such in the future.
as the cost of the products, directly impact sales in the market. Another
challenge is the time period for the development of a complete product CRediT authorship contribution statement
as per the regulatory requirements [203]. On the other hand, challenges
from consumers include a lack of sufficient knowledge of product Vivek P. Chavda: Conceptualization, Supervision, Data curation,
applicability. Labelling always contains the value of testing results of the Formal analysis, Methodology, Validation, Visualization, Writing –
specific amount of sunscreen by which proper sun protection can be original draft. Devarshi Acharya: Writing – original draft. Vivek Hala:
obtained, while consumers do not apply a sufficient amount of sunscreen Writing – original draft. Lalitkumar K. Vora: Resources, Supervision,
on the skin, which ultimately leads to less effectiveness of the formu Visualization, Writing – review & editing.
lation. Due to differences in the patient-to-patient applied quantity, it
will not produce the same effects in all patients. Another challenge is the
maintenance of the trust of consumers because not using it in the proper Declaration of competing interest
amount and adequate quantity leads to failure to produce good photo
protective effects. One of the major problems related to sunscreen for All authors declare that they have no known competing financial
mulations is that regulatory criteria are different according to country, interests or personal relationships that could have appeared to influence
which may vary the testing parameters and finally the product labelling the work reported in this paper.
conditions as well as the effectiveness of the formulations. The lack of
one international regulation criterion makes very confusing situations Data availability
for the manufacturer as well as consumers. Sunscreen products in
poor/underdeveloped countries due to a lack of sufficient sources for the No data was used for the research described in the article.
production of sunscreen formulation costs are also the same challenge
for consumers as manufacturers [255,257]. Acknowledgments
Instead of several advancements have been done in field of nano
technology and successful application in cometic field, very limited V.P.C. wants to dedicate this work to L M College of pharmacy as a
clinical trials have been conducted on sunscreen using nano part of the 75th year celebration of the college. V.P.C. is grateful to the L.
formulations. In a clinical trial, bioadhesive nanoparticles-based sun M. College of Pharmacy, Ahmedabad, India, for providing necessary
screen was developed. They claimed that developed sunscreen support in carrying out the literature search.
prevented damage caused by UV exposure through the use of a nano
particle delivery vehicle. Moreover, the bioadhesive nature provides References
longer protection. Additionally, incorporation of the UV filter in a
nanoparticle (BNP), interrupt degradation of filter, enhances photo [1] H. Hidaka, S. Horikoshi, N. Serpone, J. Knowland, In vitro photochemical damage
to DNA, RNA and their bases by an inorganic sunscreen agent on exposure to UVA
stability, and avoid reactive oxygen species (ROS), thus decreasing and UVB radiation, J. Photochem. Photobiol. Chem. 111 (1997) 205–213,
overall risk of epidermal toxicity, and cell damage (NCT02668536). https://doi.org/10.1016/S1010-6030(97)00229-3.
[2] D. Bolles, Infrared Waves | Science Mission Directorate, NASA Science, 2022.
https://science.nasa.gov/ems/07_infraredwaves. (Accessed 9 December 2022).
[3] D. Bolles, Visible Light | Science Mission Directorate, NASA Science, 2022. https
://science.nasa.gov/ems/09_visiblelight. (Accessed 9 December 2022).
22
[4] D. Bolles, Ultraviolet Waves | Science Mission Directorate, NASA Science, 2022. [32] R.C. Romanhole, A.L.M. Fava, L.L. Tundisi, L.M. de Macedo, É.M. dos Santos, J.
https://science.nasa.gov/ems/10_ultravioletwaves. (Accessed 9 December 2022). A. Ataide, P.G. Mazzola, Unplanned absorption of sunscreen ingredients: impact
[5] J. D’Orazio, S. Jarrett, A. Amaro-Ortiz, T. Scott, UV radiation and the skin, Int. J. of formulation and evaluation methods, Int. J. Pharm. 591 (2020), 120013,
Mol. Sci. 14 (2013) 12222–12248, https://doi.org/10.3390/IJMS140612222. https://doi.org/10.1016/J.IJPHARM.2020.120013.
[6] J. Cadet, T. Douki, Formation of UV-induced DNA damage contributing to skin [33] S.X. Li, M.F. Li, J. Bian, X.F. Wu, F. Peng, M.G. Ma, Preparation of organic acid
cancer development, Photochem. Photobiol. Sci. 17 (2018) 1816–1841, https:// lignin submicrometer particle as a natural broad-spectrum photo-protection
doi.org/10.1039/C7PP00395A. agent, Int. J. Biol. Macromol. 132 (2019) 836–843, https://doi.org/10.1016/J.
[7] W. Zou, M. Sastry, J.J. Gooding, R. Ramanathan, V. Bansal, Recent advances and IJBIOMAC.2019.03.177.
a roadmap to wearable UV sensor technologies, Adv. Mater. Technol. 5 (2020), [34] M.V.C. Terto, J.M. Gomes, D.I.A.F. Araújo, T.S. Silva, J.M. Ferreira, J.J.N. Souza,
1901036, https://doi.org/10.1002/ADMT.201901036. M.S. Silva, J.F. Tavares, Photoprotective activity of plectranthus amboinicus
[8] D.R. Sambandan, D. Ratner, Sunscreens: an overview and update, J. Am. Acad. extracts and HPLC quantification of rosmarinic acid, Revista Brasileira De
Dermatol. 64 (2011) 748–758, https://doi.org/10.1016/J.JAAD.2010.01.005. Farmacognosia-Brazilian Journal of Pharmacognosy 30 (2020) 183–188, https://
[9] D.G. Yeager, H.W. Lim, What’s new in photoprotection: a review of new concepts doi.org/10.1007/S43450-020-00040-6.
and controversies, Dermatol. Clin. 37 (2019) 149–157, https://doi.org/10.1016/ [35] F. Álvarez-Gómez, N. Korbee, V. Casas-Arrojo, R.T. Abdala-Díaz, F.L. Figueroa,
j.det.2018.11.003. UV photoprotection, cytotoxicity and immunology capacity of red algae extracts,
[10] R.J.B. Cordero, A. Casadevall, Melanin, Curr. Biol. 30 (2020) R142, https://doi. Molecules 24 (2019) 341, https://doi.org/10.3390/MOLECULES24020341.
org/10.1016/J.CUB.2019.12.042. –R143. [36] S.K. Shanuja, S. Iswarya, A. Gnanamani, Marine fungal DHICA as a UVB
[11] H.R. Taylor, Ultraviolet radiation and the eye: an epidemiologic study, Trans. Am. protectant: assessment under in vitro and in vivo conditions, J. Photochem.
Ophthalmol. Soc. 87 (1989) 853. /pmc/articles/PMC1298564/?report=abstract. Photobiol., B 179 (2018) 139–148, https://doi.org/10.1016/J.
(Accessed 9 November 2022). JPHOTOBIOL.2018.01.010.
[12] J. Krutmann, A. Bouloc, G. Sore, B.A. Bernard, T. Passeron, The skin aging [37] L.C. Tomazelli, M.M. de Assis Ramos, R. Sauce, T.M. Cândido, F.D. Sarruf, C.A.
exposome, J. Dermatol. Sci. 85 (2017) 152–161, https://doi.org/10.1016/J. S. de Oliveira Pinto, C.A. de Oliveira, C. Rosado, M.V.R. Velasco, A.R. Baby, SPF
JDERMSCI.2016.09.015. enhancement provided by rutin in a multifunctional sunscreen, Int. J. Pharm. 552
[13] A. Juzeniene, J. Moan, Beneficial effects of UV radiation other than via vitamin D (2018) 401–406, https://doi.org/10.1016/j.ijpharm.2018.10.015.
production, Derm. Endocrinol. 4 (2012) 109–117, https://doi.org/10.4161/ [38] D.D.A. Peres, F.D. Sarruf, C.A. de Oliveira, M.V.R. Velasco, A.R. Baby, Ferulic acid
DERM.20013. http://http//Www.Tandfonline.Com/Action/AuthorSubmission? photoprotective properties in association with UV filters: multifunctional
JournalCode=kder20&page=instructions. sunscreen with improved SPF and UVA-PF, J. Photochem. Photobiol., B 185
[14] T. Bintsis, E. Litopoulou-Tzanetaki, R. Davies, R.K. Robinson, The antimicrobial (2018) 46–49, https://doi.org/10.1016/J.JPHOTOBIOL.2018.05.026.
effects of long-wave ultra-violet light and furocoumarins on some micro- [39] A.L. Morocho-Jácome, T.B. Freire, A.C. de Oliveira, T.S. de Almeida, C. Rosado,
organisms that occur in cheese brines, Food Microbiol. 17 (2000) 687–695, M.V.R. Velasco, A.R. Baby, In vivo SPF from multifunctional sunscreen systems
https://doi.org/10.1006/FMIC.2000.0370. developed with natural compounds—a review, J. Cosmet. Dermatol. 20 (2021)
[15] N. Fleury, S. Geldenhuys, S. Gorman, D. Haluza, S. Simic, H. Moshammer, Sun 729–737, https://doi.org/10.1111/JOCD.13609.
exposure and its effects on human health: mechanisms through which sun [40] C. Rosado, V.K. Tokunaga, R. Sauce, C.A. De Oliveira, F.D. Sarruf, R. Parise-Filho,
exposure could reduce the risk of developing obesity and cardiometabolic E. Maurício, T.S. De Almeida, M.V.R. Velasco, A.R. Baby, Another reason for
dysfunction, Int. J. Environ. Res. Publ. Health 13 (2016) 999, https://doi.org/ using caffeine in dermocosmetics: sunscreen adjuvant, Front. Physiol. 10 (2019)
10.3390/IJERPH13100999. 519, https://doi.org/10.3389/FPHYS.2019.00519/BIBTEX.
[16] R.B. Weller, Sunlight has cardiovascular benefits independently of vitamin D, [41] A.A. Hübner, F.D. Sarruf, C.A. Oliveira, A.V. Neto, D.C.H. Fischer, E.T.M. Kato, F.
Blood Purif. 41 (2016) 130–134, https://doi.org/10.1159/000441266. R. Lourenço, A.R. Baby, E.M. Bacchi, Safety and photoprotective efficacy of a
[17] SunSmart position statement | Cancer Council, (n.d.). https://www.cancer.org. sunscreen system based on grape pomace (Vitis vinifera L.) phenolics from
au/about-us/policy-and-advocacy/position-statements/sunsmart (accessed winemaking, Pharmaceutics 12 (2020) 1148, https://doi.org/10.3390/
November 9, 2022). PHARMACEUTICS12121148.
[18] A.C. Green, G.M. Williams, V. Logan, G.M. Strutton, Reduced melanoma after [42] K.B. Wróblewska, A.R. Baby, M.T. Grombone Guaratini, P.R.H. Moreno, In vitro
regular sunscreen use: randomized trial follow-up, J. Clin. Oncol. 29 (2011) antioxidant and photoprotective activity of five native Brazilian bamboo species,
257–263, https://doi.org/10.1200/JCO.2010.28.7078. Ind. Crop. Prod. 130 (2019) 208–215, https://doi.org/10.1016/J.
[19] F.D. Kabigting, F.P. Nelson, C.L. Kauffman, G. Popoveniuc, C.A. Dasanu, D. INDCROP.2018.12.081.
T. Alexandrescu, Malignant melanoma in African Americans, Dermatol. Online J. [43] Cosmetics Market Size, Growth | Global Industry Analysis, 2028, (n.d.). http
15 (2009) 403–404, https://doi.org/10.5070/D33K77P755. s://www.fortunebusinessinsights.com/cosmetics-market-102614 (accessed
[20] K. Suozzi, J. Turban, M. Girardi, Focus: skin: cutaneous photoprotection: a review November 9, 2022).
of the current status and evolving strategies, Yale J. Biol. Med. 93 (2020) 67. [44] A. Gautam, D. Singh, R. Vijayaraghavan, Dermal exposure of nanoparticles: an
/pmc/articles/PMC7087054/. (Accessed 9 November 2022). understanding, Antoniorondonlugo.Com. 11 (2011) 2703–2708. https://anton
[21] T. Maier, H.C. Korting, Sunscreens – which and what for? Skin Pharmacol. iorondonlugo.com/wp-content/uploads/2016/01/36.-Gautam-Review.pdf.
Physiol. 18 (2005) 253–262, https://doi.org/10.1159/000087606. (Accessed 9 November 2022).
[22] E. Scheuer, E. Warshaw, Sunscreen allergy: a review of epidemiology, clinical [45] Summary of Cosmetics Labeling Requirements | FDA, (n.d.). https://www.fda.go
characteristics, and responsible allergens, Dermatitis 17 (2006) 3–11, https://doi. v/cosmetics/cosmetics-labeling-regulations/summary-cosmetics-labeling-require
org/10.2310/6620.2006.05017. ments (accessed November 9, 2022).
[23] Federal Register :: Sunscreen Drug Products for Over-the-Counter Human Use, (n. [46] V. Dhapte-Pawar, S. Kadam, S. Saptarsi, P.P. Kenjale, Nanocosmeceuticals: facets
d.). https://www.federalregister.gov/documents/2019/02/26/2019-03019/sun and aspects, Future Sci OA 6 (2020), https://doi.org/10.2144/FSOA-2019-0109/
screen-drug-products-for-over-the-counter-human-use (accessed November 9, ASSET/IMAGES/LARGE/FIGURE5.JPEG.
2022). [47] A.D. Gholap, S.F. Sayyad, N.T. Hatvate, V.V. Dhumal, S.R. Pardeshi, V.P. Chavda,
[24] Cosmetics-uv-filters - ECHA, (n.d.). https://echa.europa.eu/cosmetics-uv-filters L.K. Vora, Drug delivery strategies for avobenzone: a case study of
(accessed November 9, 2022). photostabilization, Pharmaceutics 15 (2023) 1008, https://doi.org/10.3390/
[25] Australian regulatory guidelines for sunscreens (ARGS) | Therapeutic Goods pharmaceutics15031008.
Administration (TGA), (n.d.). https://www.tga.gov.au/resources/publication/pu [48] A.C. Santos, F. Morais, A. Simões, I. Pereira, J.A.D. Sequeira, M. Pereira-Silva,
blications/australian-regulatory-guidelines-sunscreens-args (accessed November F. Veiga, A. Ribeiro, Nanotechnology for the development of new cosmetic
9, 2022). formulations, Expet Opin. Drug Deliv. (2019) 313–330, https://doi.org/10.1080/
[26] A.C. Santos, J. Marto, R. Chá-Chá, A.M. Martins, M. Pereira-Silva, H.M. Ribeiro, 17425247.2019.1585426.
F. Veiga, Nanotechnology-based sunscreens—a review, Mater. Today Chem. 23 [49] S. Dhawan, P. Sharma, S. Nanda, Cosmetic nanoformulations and their intended
(2022), 100709, https://doi.org/10.1016/J.MTCHEM.2021.100709. use, in: Slimani Yassine (Ed.), Nanda Arun, Nanda Sanju, Rajendran Susai,
[27] S.Q. Wang, I.R. Tooley, Photoprotection in the era of nanotechnology, Semin. Nguyen Anh Tuan, Nanocosmetics, Elsevier, 2020, pp. 141–169, https://doi.org/
Cutan. Med. Surg. 30 (2011) 210–213, https://doi.org/10.1016/J. 10.1016/B978-0-12-822286-7.00017-6.
SDER.2011.07.006. [50] M.N. Abu Hajleh, R. Abu-Huwaij, A. AL-Samydai, L.K. Al-Halaseh, E.A. Al-Dujaili,
[28] W. Stahl, H. Sies, β-Carotene and other carotenoids in protection from sunlight, The revolution of cosmeceuticals delivery by using nanotechnology: a narrative
Am. J. Clin. Nutr. 96 (2012) 1179S–1184S, https://doi.org/10.3945/ review of advantages and side effects, J. Cosmet. Dermatol. 20 (2021)
AJCN.112.034819. 3818–3828, https://doi.org/10.1111/JOCD.14441.
[29] J.M.T. de A. Filho, P.A. Sampaio, E.C.V. Pereira, R.G. de O. Jonior, F.S. Silva, , J. [51] L.J. Mortensen, G. Oberdörster, A.P. Pentland, L.A. DeLouise, In vivo skin
R.G. da S. Almeida, L.A. Rolim, X.P. Nunes, E.C. da C. Araojo, Flavonoids as penetration of quantum dot nanoparticles in the murine model: the effect of UVR,
photoprotective agents: a systematic review, J. Med. Plants Res. 10 (2016) Nano Lett. 8 (2008) 2779–2787, https://doi.org/10.1021/NL801323Y/SUPPL_
848–864, https://doi.org/10.5897/JMPR2016.6273. FILE/NL801323Y-FILE002.PDF.
[30] L. Chen, J.Y. Hu, S.Q. Wang, The role of antioxidants in photoprotection: a critical [52] B. Iqbal, J. Ali, S. Baboota, Recent advances and development in epidermal and
review, J. Am. Acad. Dermatol. 67 (2012) 1013–1024, https://doi.org/10.1016/ dermal drug deposition enhancement technology, Int. J. Dermatol. 57 (2018)
J.JAAD.2012.02.009. 646–660, https://doi.org/10.1111/IJD.13902.
[31] hailun He, anqi Li, shiqin Li, jie Tang, li Li, lidan Xiong, Natural components in [53] S. Contera, J.B. de La Serna, T.D. Tetley, Biotechnology, nanotechnology and
sunscreens: topical formulations with sun protection factor (SPF), Biomed. medicine, Emerg Top Life Sci 4 (2020) 551, https://doi.org/10.1042/
Pharmacother. 134 (2021), 111161, https://doi.org/10.1016/J. ETLS20200350.
BIOPHA.2020.111161.
23
[54] T.A. Nuzhatun Nisa, Therapeutic and diagnostic applications of nanotechnology capabilities: preparation, characterization and in vivo evaluation, Expet Opin.
in dermatology and cosmetics, J. Nanomed. Biother. Discov. 5 (2015), https:// Drug Deliv. 10 (2013) 411–420, https://doi.org/10.1517/
doi.org/10.4172/2155-983X.1000134. 17425247.2013.749234.
[55] D. Nesseem, Formulation of sunscreens with enhancement sun protection factor [79] L.A. Balestrin, J. Bidone, R.C. Bortolin, K. Moresco, J.C. Moreira, H.F. Teixeira,
response based on solid lipid nanoparticles, Int. J. Cosmet. Sci. 33 (2011) 70–79, Protective effect of a hydrogel containing Achyrocline satureioides extract-loaded
https://doi.org/10.1111/J.1468-2494.2010.00598.X. nanoemulsion against UV-induced skin damage, J. Photochem. Photobiol., B 163
[56] M. Kumud, N. Sanju, Nanotechnology driven cosmetic products: commercial and (2016) 269–276, https://doi.org/10.1016/J.JPHOTOBIOL.2016.08.039.
regulatory milestones, Applied Clinical Research, Clinical Trials and Regulatory [80] P.K. Shetty, V. Venuvanka, H.V. Jagani, G.H. Chethan, V.S. Ligade, P.
Affairs 5 (2018) 112–121, https://doi.org/10.2174/ B. Musmade, U.Y. Nayak, M.S. Reddy, G. Kalthur, N. Udupa, C.M. Rao, S. Mutalik,
2213476X05666180530093111. Development and evaluation of sunscreen creams containing morin-encapsulated
[57] A.L. Vasilakes, T.D. Dziubla, P.P. Wattamwar, Polymeric Nanoparticles, nanoparticles for enhanced UV radiation protection and antioxidant activity, Int.
Engineering Polymer Systems for Improved Drug Delivery, vol. 9781118098479, J. Nanomed. 10 (2015) 6491, https://doi.org/10.2147/IJN.S90964.
2013, pp. 117–161, https://doi.org/10.1002/9781118747896.CH5. [81] H. Joshi, A.R. Hegde, P.K. Shetty, H. Gollavilli, R.S. Managuli, G. Kalthur,
[58] E. Ratemi, A. Sultana Shaik, A. al Faraj, R. Halwani, Alternative approaches for S. Mutalik, Sunscreen creams containing naringenin nanoparticles: formulation
the treatment of airway diseases: focus on nanoparticle medicine, Clin. Exp. development and in vitro and in vivo evaluations, Photodermatol.
Allergy 46 (2016) 1033–1042, https://doi.org/10.1111/CEA.12771. Photoimmunol. Photomed. 34 (2018) 69–81, https://doi.org/10.1111/
[59] B.V.N. Nagavarma, H. Yadav, A. Ayaz, L.S. Vasudha, Different techniques for PHPP.12335.
preparation of polymeric nanoparticles- A review | Request PDF, Asian Journal of [82] M.S. Frizzo, P.E. Feuser, P.H. Berres, E. Ricci-Júnior, C.E.M. Campos, C. Costa, P.
Pharmaceutical and Clinical 5 (2012) 16–23. https://www.researchgate. H.H. de Araújo, C. Sayer, Simultaneous encapsulation of zinc oxide and
net/publication/279545193_Different_techniques_for_preparation_of_polymeric octocrylene in poly (methyl methacrylate-co-styrene) nanoparticles obtained by
_nanoparticles-_A_review. (Accessed 11 November 2022). miniemulsion polymerization for use in sunscreen formulations, Colloids Surf. A
[60] A. Gupta, Nanoemulsions, in: Nanoparticles for Biomedical Applications: Physicochem. Eng. Asp. 561 (2019) 39–46, https://doi.org/10.1016/J.
Fundamental Concepts, Biological Interactions and Clinical Applications, COLSURFA.2018.10.062.
Elsevier, 2020, pp. 371–384, https://doi.org/10.1016/B978-0-12-816662- [83] N. Andréo-Filho, A.V.K. Bim, T.M. Kaneko, N.A. Kitice, I.N. Haridass, E. Abd,
8.00021-7. P. Santos Lopes, S.S. Thakur, H.S. Parekh, M.S. Roberts, J.E. Grice, H.A.E. Benson,
[61] R. Bhosale, R. Osmani, Ghodake PP, Shaikh SM, Chavan SR, Nanoemulsion: A V.R. Leite-Silva, Development and evaluation of lipid nanoparticles containing
review on novel profusion in advanced drug delivery, Indian J. Pharmaceut. Biol. natural botanical oil for sun protection: characterization and in vitro and in vivo
Res. . 2 (2014) 122–127. https://www.academia.edu/download/86844471/28c human skin permeation and toxicity, Skin Pharmacol. Physiol. 31 (2018) 1–9,
ea60e1aaef87f1cca9a0ac8ce91bfd9e6.pdf (accessed November 10, 2022). https://doi.org/10.1159/000481691.
[62] V. Gupta, S. Mohapatra, H. Mishra, U. Farooq, K. Kumar, M.J. Ansari, M. [84] G. Netto Mpharm, J. Jose, Development, characterization, and evaluation of
F. Aldawsari, A.S. Alalaiwe, M.A. Mirza, Z. Iqbal, Nanotechnology in cosmetics sunscreen cream containing solid lipid nanoparticles of silymarin, J. Cosmet.
and cosmeceuticals—a review of latest advancements, Gels 8 (2022) 173, https:// Dermatol. 17 (2018) 1073–1083, https://doi.org/10.1111/JOCD.12470.
doi.org/10.3390/GELS8030173. [85] M.S. Berkman, Y. Yazan, Solid lipid nanoparticles: a possible vehicle for zinc
[63] C. Bharti, U. Nagaich, A.K. Pal, N. Gulati, Mesoporous silica nanoparticles in oxide and octocrylene, Die Pharmazie - An International Journal of
target drug delivery system: a review, Int J Pharm Investig 5 (2015) 133, https:// Pharmaceutical Sciences 67 (2012) 202–208, https://doi.org/10.1691/
doi.org/10.4103/2230-973X.160844. PH.2012.1098.
[64] R. Parhi, P. Suresh, Preparation and characterization of solid lipid nanoparticles- [86] C.S. Cerqueira-Coutinho, V.E.B. de Campo, A.L. Rossi, V.F. Veiga, C. Holandino,
A review, Curr. Drug Discov. Technol. 9 (2012) 2–16, https://doi.org/10.2174/ Z.M.F. Freitas, E. Ricci-Junior, C.R.E. Mansur, E.P. Santos, R. Santos-Oliveira,
157016312799304552. Comparing in vivo biodistribution with radiolabeling and Franz cell permeation
[65] I. Chauhan, M. Yasir, M. Verma, A.P. Singh, Nanostructured lipid carriers: a assay to validate the efficacy of both methodologies in the evaluation of
groundbreaking approach for transdermal drug delivery, Adv. Pharmaceut. Bull. nanoemulsions: a safety approach, Nanotechnology 27 (2015), 015101, https://
10 (2020) 150–165, https://doi.org/10.34172/apb.2020.021. doi.org/10.1088/0957-4484/27/1/015101.
[66] G. Liu, S. Hou, P. Tong, J. Li, Liposomes: preparation, characteristics, and [87] R.K. Harwansh, P.K. Mukherjee, A. Kar, S. Bahadur, N.A. Al-Dhabi,
application strategies in Analytical chemistry, Crit. Rev. Anal. Chem. 52 (2022) V. Duraipandiyan, Enhancement of photoprotection potential of catechin loaded
392–412, https://doi.org/10.1080/10408347.2020.1805293. nanoemulsion gel against UVA induced oxidative stress, J. Photochem.
[67] C. Oliveira, C. Coelho, J.A. Teixeira, P. Ferreira-Santos, C.M. Botelho, Photobiol., B 160 (2016) 318–329, https://doi.org/10.1016/J.
Nanocarriers as active ingredients enhancers in the cosmetic industry—the JPHOTOBIOL.2016.03.026.
European and North America regulation challenges, Molecules 27 (2022) 1669, [88] I. Hanno, C. Anselmi, K. Bouchemal, Polyamide nanocapsules and nano-
https://doi.org/10.3390/MOLECULES27051669. emulsions containing Parsol® MCX and Parsol® 1789: in vitro release, ex vivo
[68] Chavda Vivek, niosome: a vesicular weapon for targeted and controlled drug skin penetration and photo-stability studies, Pharmaceut. Res. 29 (2011)
delivery, Indian J. Nov. Drug Deliv. (2016) 133–156. https://www.researchgate. 559–573, https://doi.org/10.1007/S11095-011-0592-5.
net/publication/313360483_niosome_a_vesicular_weapon_for_targeted_and_con [89] K.S. Avadhani, J. Manikkath, M. Tiwari, M. Chandrasekhar, A. Godavarthi, S.
trolled_drug_delivery. (Accessed 10 November 2022). M. Vidya, R.C. Hariharapura, G. Kalthur, N. Udupa, S. Mutalik, Skin delivery of
[69] F.F.F. Silva, E. Ricci-Júnior, C.R.E. Mansur, Nanoemulsions containing octyl epigallocatechin-3-gallate (EGCG) and hyaluronic acid loaded nano-
methoxycinnamate and solid particles of TiO2: preparation, characterization and transfersomes for antioxidant and anti-aging effects in UV radiation induced skin
in vitro evaluation of the solar protection factor, Drug Dev. Ind. Pharm. 39 (2013) damage, Drug Deliv. 24 (2017) 61–74, https://doi.org/10.1080/
1378–1388, https://doi.org/10.3109/03639045.2012.718787. 10717544.2016.1228718.
[70] I. Kaur, R. Agrawal, Nanotechnology: a new paradigm in cosmeceuticals, Recent [90] C.D. Kaur, S. Saraf, Topical vesicular formulations of Curcuma longa extract on
Pat. Drug Deliv. Formulation 1 (2007) 171–182, https://doi.org/10.2174/ recuperating the ultraviolet radiation–damaged skin, J. Cosmet. Dermatol. 10
187221107780831888. (2011) 260–265, https://doi.org/10.1111/J.1473-2165.2011.00586.X.
[71] Y. Wu, Y.H. Li, X.H. Gao, H.D. Chen, The application of nanoemulsion in [91] A. Ascenso, S. Raposo, C. Batista, P. Cardoso, T. Mendes, F.G. Praça, M.V.L.
dermatology: an overview, J. Drug Target. 21 (2013) 321–327, https://doi.org/ B. Bentley, S. Simões, Development, characterization, and skin delivery studies of
10.3109/1061186X.2013.765442. related ultradeformable vesicles: transfersomes, ethosomes, and transethosomes,
[72] V. Bali, M. Ali, J. Ali, Study of surfactant combinations and development of a Int. J. Nanomed. 10 (2015) 5851, https://doi.org/10.2147/IJN.S86186.
novel nanoemulsion for minimising variations in bioavailability of ezetimibe, [92] G. Niculae, I. Lacatusu, N. Badea, A. Meghea, Lipid nanoparticles based on butyl-
Colloids Surf. B Biointerfaces 76 (2010) 410–420, https://doi.org/10.1016/J. methoxydibenzoylmethane: in vitro UVA blocking effect, Nanotechnology 23
COLSURFB.2009.11.021. (2012), 315704, https://doi.org/10.1088/0957-4484/23/31/315704.
[73] T. Tadros, Application of rheology for assessment and prediction of the long-term [93] S. Nikolić, C.M. Keck, C. Anselmi, R.H. Müller, Skin photoprotection
physical stability of emulsions, Adv. Colloid Interface Sci. 108–109 (2004) improvement: synergistic interaction between lipid nanoparticles and organic UV
227–258, https://doi.org/10.1016/J.CIS.2003.10.025. filters, Int. J. Pharm. 414 (2011) 276–284, https://doi.org/10.1016/J.
[74] A. Juzeniene, J. Moan, Beneficial effects of UV radiation other than via vitamin D IJPHARM.2011.05.010.
production, Derm. Endocrinol. 4 (2012) 109–117, https://doi.org/10.4161/ [94] N. Knežević, N. Ilić, V. Dokić, R. Petrović, D. Janaćković, Mesoporous silica and
DERM.20013. http://www.tandfonline.com/Action/AuthorSubmission?Journ organosilica nanomaterials as UV-blocking agents, ACS Appl. Mater. Interfaces 10
alCode=kder20&page=instructions. (2018) 20231–20236, https://doi.org/10.1021/ACSAMI.8B04635/SUPPL_FILE/
[75] P. Boonme, S. Yotsawimonwat, Anti-ageing microemulsions and nanoemulsions, AM8B04635_SI_001.PDF.
HPC Today 6 (2011) 42–46. https://www.teknoscienze.com/tks_article/anti-agei [95] Z. Zhang, B. Zhang, N. Grishkewich, R. Berry, K.C. Tam, Cinnamate-
ng-microemulsions-and-nanoemulsions/. (Accessed 11 November 2022). functionalized cellulose nanocrystals as UV-shielding Nanofillers in sunscreen
[76] M.I. Nasiri, L.K. Vora, J.A. Ershaid, K. Peng, I.A. Tekko, R.F. Donnelly, and transparent polymer films, Adv Sustain Syst 3 (2019), 1800156, https://doi.
Nanoemulsion-based dissolving microneedle arrays for enhanced intradermal and org/10.1002/ADSU.201800156.
transdermal delivery, Drug Deliv. Transl. Res. 12 (2022) 881–896. [96] L. al Shaal, R. Shegokar, R.H. Müller, Production and characterization of
[77] T.H. Kabri, E. Arab-Tehrany, N. Belhaj, M. Linder, Physico-chemical antioxidant apigenin nanocrystals as a novel UV skin protective formulation, Int.
characterization of nano-emulsions in cosmetic matrix enriched on omega-3, J. Pharm. 420 (2011) 133–140, https://doi.org/10.1016/J.
J. Nanobiotechnol. 9 (2011) 1–8, https://doi.org/10.1186/1477-3155-9-41/ IJPHARM.2011.08.018.
FIGURES/3. [97] A. de C.V. Mota, Z.M.F. de Freitas, E. Júnior Ricci, G.M. Dellamora-Ortiz,
[78] S. Dasgupta, S. Dey, S. Choudhury, B. Mazumder, Topical delivery of aceclofenac R. Santos-Oliveira, R.A. Ozzetti, A. Luiz Vergnanini, V. Lira Ribeiro, R. Santos
as nanoemulsion comprising excipients having optimum emulsification Silva, E. Pereira dos Santos, In vivo and in vitro evaluation of octyl
24
methoxycinnamate liposomes, Int. J. Nanomed. 8 (2013) 4689–4700, https://doi. melanoma management, Int. J. Pharmaceut. 627 (2022), 122217, https://doi.
org/10.2147/IJN.S51383. org/10.1016/j.ijpharm.2022.122217.
[98] M. Sato de Souza de Bustamante Monteiro, R. Antonio Ozzetti, A. Luiz [122] A. Laouini, C. Jaafar-Maalej, I. Limayem-Blouza, S. Sfar, C. Charcosset, H. Fessi,
Vergnanini, L. de Brito-Gitirana, N. Maria Volpato, Z. Maria Faria de Freitas, Preparation, characterization and applications of liposomes: state of the art,
E. Ricci-Júnior, E. Pereira dos Santos, Evaluation of octyl p-methoxycinnamate Journal of Colloid Science and Biotechnology 1 (2012) 147–168, https://doi.org/
included in liposomes and cyclodextrins in anti-solar preparations: preparations, 10.1166/JCSB.2012.1020.
characterizations and in vitro penetration studies, Int. J. Nanomed. 7 (2012) [123] D. Papakostas, F. Rancan, W. Sterry, U. Blume-Peytavi, A. Vogt, Nanoparticles in
3045–3058, https://doi.org/10.2147/IJN.S28550. dermatology, Arch. Dermatol. Res. 303 (2011) 533–550, https://doi.org/
[99] D.R. Sambandan, D. Ratner, Sunscreens: an overview and update, J. Am. Acad. 10.1007/S00403-011-1163-7.
Dermatol. 64 (2011) 748–758, https://doi.org/10.1016/J.JAAD.2010.01.005. [124] J. Brewer, M. Bloksgaard, J. Kubiak, J.A. Sørensen, L.A. Bagatolli, Spatially
[100] D. Ainbinder, E. Touitou, Skin photodamage prevention: state of the art and new resolved two-color diffusion measurements in human skin applied to transdermal
prospects, in: Textbook of Aging Skin, Springer Berlin Heidelberg, 2010, liposome penetration, J. Invest. Dermatol. 133 (2013) 1260–1268, https://doi.
pp. 429–440, https://doi.org/10.1007/978-3-540-89656-2_44/COVER. org/10.1038/JID.2012.461.
[101] C. Antoniou, M.G. Kosmadaki, A.J. Stratigos, A.D. Katsambas, Sunscreens – [125] E.H. Gökçe, E.A. Yapar, S.T. Tanriverdi, özgen özer, in: Nanocarriers in
what’s important to know, J. Eur. Acad. Dermatol. Venereol. 22 (2008) Cosmetology, Nanobiomaterials in Galenic Formulations and Cosmetics:
1110–1119, https://doi.org/10.1111/J.1468-3083.2007.02580.X. Applications of Nanobiomaterials, 2016, pp. 363–393, https://doi.org/10.1016/
[102] E.L. Romero, M.J. Morilla, Highly deformable and highly fluid vesicles as B978-0-323-42868-2.00014-0.
potential drug delivery systems: theoretical and practical considerations, Int. J. [126] S. Dhawan, P. Sharma, S. Nanda, Cosmetic nanoformulations and their intended
Nanomed. 8 (2013) 3171–3186, https://doi.org/10.2147/IJN.S33048. use, in: Nanocosmetics, Elsevier, 2020, pp. 141–169, https://doi.org/10.1016/
[103] L.M. Katz, K. Dewan, R.L. Bronaugh, Nanotechnology in cosmetics, Food Chem. B978-0-12-822286-7.00017-6.
Toxicol. 85 (2015) 127–137, https://doi.org/10.1016/J.FCT.2015.06.020. [127] N.S. Raju, V. Krishnaswami, S. Vijayaraghavalu, R. Kandasamy, Transdermal and
[104] S.A.T. Opatha, V. Titapiwatanakun, R. Chutoprapat, Transfersomes: a promising bioactive nanocarriers, in: Nanocosmetics, Elsevier, 2020, pp. 17–33, https://doi.
Nanoencapsulation technique for transdermal drug delivery, Pharmaceutics 12 org/10.1016/B978-0-12-822286-7.00002-4.
(2020) 1–23, https://doi.org/10.3390/PHARMACEUTICS12090855. [128] C. Cerqueira, F. Nigro, V.E.B. Campos, A. Rossi, R. Santos-Oliveira, V. Cardoso, A.
[105] J. Chen, W.L. Lu, W. Gu, S.S. Lu, Z.P. Chen, B.C. Cai, Skin permeation behavior of B. Vermelho, E.P. dos Santos, C.R.E. Mansur, Nanovesicle-based formulations for
elastic liposomes: role of formulation ingredients, Expet Opin. Drug Deliv. 10 photoprotection: a safety and efficacy approach, Nanotechnology 30 (2019),
(2013) 845–856, https://doi.org/10.1517/17425247.2013.779252. 345102, https://doi.org/10.1088/1361-6528/AB177C.
[106] N. Dragicevic-Curic, S. Gräfe, B. Gitter, S. Winter, A. Fahr, Surface charged [129] M.A. Gwak, B.M. Hong, W.H. Park, Hyaluronic acid/tannic acid hydrogel
temoporfin-loaded flexible vesicles: in vitro skin penetration studies and stability, sunscreen with excellent anti-UV, antioxidant, and cooling effects, Int. J. Biol.
Int. J. Pharm. 384 (2010) 100–108, https://doi.org/10.1016/J. Macromol. 191 (2021) 918–924, https://doi.org/10.1016/J.
IJPHARM.2009.10.006. IJBIOMAC.2021.09.169.
[107] S. Prikhnenko, Polycomponent mesotherapy formulations for the treatment of [130] B. Faure, G. Salazar-Alvarez, A. Ahniyaz, I. Villaluenga, G. Berriozabal, Y.R. de
skin aging and improvement of skin quality, Clin. Cosmet. Invest. Dermatol. 8 Miguel, L. Bergström, Dispersion and surface functionalization of oxide
(2015) 157, https://doi.org/10.2147/CCID.S76721. nanoparticles for transparent photocatalytic and UV-protecting coatings and
[108] M. Yamaguchi, Y. Tahara, T. Makino, T. Shimizu, A. Date, Comparison of sunscreens, Sci. Technol. Adv. Mater. 14 (2013), 023001, https://doi.org/
cathepsin L activity in cheek and forearm stratum corneum in young female 10.1088/1468-6996/14/2/023001.
adults, Skin Res. Technol. 15 (2009) 370–375, https://doi.org/10.1111/J.1600- [131] P. Severino, T. Andreani, A. Jäger, M.v. Chaud, M.H.A. Santana, A.M. Silva, E.
0846.2009.00373.X. B. Souto, Solid lipid nanoparticles for hydrophilic biotech drugs: optimization and
[109] M. Ramos-e-Silva, S.C. da Silva Carneiro, Elderly skin and its rejuvenation: cell viability studies (Caco-2 & HEPG-2 cell lines), Eur. J. Med. Chem. 81 (2014)
products and procedures for the aging skin, J. Cosmet. Dermatol. 6 (2007) 40–50, 28–34, https://doi.org/10.1016/J.EJMECH.2014.04.084.
https://doi.org/10.1111/J.1473-2165.2007.00289.X. [132] J.E.N. Dolatabadi, H. Hamishehkar, H. Valizadeh, Development of dry powder
[110] A.C. Menezes, P.M. Campos, C. Euletério, S. Simões, F.S.G. Praça, M.V.L. inhaler formulation loaded with alendronate solid lipid nanoparticles: solid-state
B. Bentley, A. Ascenso, Development and characterization of novel 1-(1- characterization and aerosol dispersion performance, Drug Dev. Ind. Pharm. 41
Naphthyl)piperazine-loaded lipid vesicles for prevention of UV-induced skin (2014) 1431–1437, https://doi.org/10.3109/03639045.2014.956111.
inflammation, Eur. J. Pharm. Biopharm. 104 (2016) 101–109, https://doi.org/ [133] K.M. Hosny, B.M. Aljaeid, Sildenafil citrate as oral solid lipid nanoparticles: a
10.1016/J.EJPB.2016.04.023. novel formula with higher bioavailability and sustained action for treatment of
[111] G. Cevc, U. Vierl, Nanotechnology and the transdermal route: a state of the art erectile dysfunction, Expet Opin. Drug Deliv. 11 (2014) 1015–1022, https://doi.
review and critical appraisal, J. Contr. Release 141 (2010) 277–299, https://doi. org/10.1517/17425247.2014.912212.
org/10.1016/J.JCONREL.2009.10.016. [134] L. Becker Peres, L. Becker Peres, P.H.H. de Araújo, C. Sayer, Solid lipid
[112] E. Touitou, N. Dayan, L. Bergelson, B. Godin, M. Eliaz, Ethosomes — novel nanoparticles for encapsulation of hydrophilic drugs by an organic solvent free
vesicular carriers for enhanced delivery: characterization and skin penetration double emulsion technique, Colloids Surf. B Biointerfaces 140 (2016) 317–323,
properties, J. Contr. Release 65 (2000) 403–418, https://doi.org/10.1016/S0168- https://doi.org/10.1016/J.COLSURFB.2015.12.033.
3659(99)00222-9. [135] J.F. Fangueiro, T. Andreani, M.A. Egea, M.L. Garcia, S.B. Souto, A.M. Silva, E.
[113] S. Jain, N. Patel, P. Madan, S. Lin, Quality by design approach for formulation, B. Souto, Design of cationic lipid nanoparticles for ocular delivery: development,
evaluation and statistical optimization of diclofenac-loaded ethosomes via characterization and cytotoxicity, Int. J. Pharm. 461 (2014) 64–73, https://doi.
transdermal route, Pharmaceut. Dev. Technol. 20 (2015) 473–489, https://doi. org/10.1016/J.IJPHARM.2013.11.025.
org/10.3109/10837450.2014.882939. [136] J.F. Fangueiro, T. Andreani, L. Fernandes, M.L. Garcia, M.A. Egea, A.M. Silva, E.
[114] M.K. Chourasia, L. Kang, S.Y. Chan, Nanosized ethosomes bearing ketoprofen for B. Souto, Physicochemical characterization of epigallocatechin gallate lipid
improved transdermal delivery, Results Pharma Sci 1 (2011) 60–67, https://doi. nanoparticles (EGCG-LNs) for ocular instillation, Colloids Surf. B Biointerfaces
org/10.1016/J.RINPHS.2011.10.002. 123 (2014) 452–460, https://doi.org/10.1016/J.COLSURFB.2014.09.042.
[115] M.M.A. Elsayed, O.Y. Abdallah, V.F. Naggar, N.M. Khalafallah, Deformable [137] J. Jose, G. Netto, Role of solid lipid nanoparticles as photoprotective agents in
liposomes and ethosomes: mechanism of enhanced skin delivery, Int. J. Pharm. cosmetics, J. Cosmet. Dermatol. 18 (2019) 315–321, https://doi.org/10.1111/
322 (2006) 60–66, https://doi.org/10.1016/J.IJPHARM.2006.05.027. JOCD.12504.
[116] E. Touitou, B. Godin, Skin nonpenetrating sunscreens for cosmetic and [138] J. Pardeike, A. Hommoss, R.H. Müller, Lipid nanoparticles (SLN, NLC) in cosmetic
pharmaceutical formulations, Clin. Dermatol. 26 (2008) 375–379, https://doi. and pharmaceutical dermal products, Int. J. Pharm. 366 (2009) 170–184, https://
org/10.1016/J.CLINDERMATOL.2008.01.014. doi.org/10.1016/J.IJPHARM.2008.10.003.
[117] I.M. Abdulbaqi, Y. Darwis, N.A.K. Khan, R.A. Assi, A.A. Khan, Ethosomal [139] C. Puglia, F. Bonina, Lipid nanoparticles as novel delivery systems for cosmetics
nanocarriers: the impact of constituents and formulation techniques on ethosomal and dermal pharmaceuticals, Expet Opin. Drug Deliv. 9 (2012) 429–441, https://
properties, in vivo studies, and clinical trials, Int. J. Nanomed. 11 (2016) 2279, doi.org/10.1517/17425247.2012.666967.
https://doi.org/10.2147/IJN.S105016. [140] L. Vora, P. Vavia, Zero order controlled release delivery of cholecalciferol from
[118] V. Garg, H. Singh, A. Bhatia, K. Raza, S.K. Singh, B. Singh, S. Beg, Systematic injectable biodegradable microsphere: In-vitro characterization and in-vivo
development of transethosomal gel system of piroxicam: formulation pharmacokinetic studies, Eur. J. Pharmaceut. Sci. 107 (2017) 78–86, https://doi.
optimization, in vitro evaluation, and ex vivo assessment, AAPS PharmSciTech 18 org/10.1016/j.ejps.2017.06.027.
(2017) 58–71, https://doi.org/10.1208/S12249-016-0489-Z/FIGURES/9. [141] D. Papakostas, F. Rancan, W. Sterry, U. Blume-Peytavi, A. Vogt, Nanoparticles in
[119] C.K. Song, P. Balakrishnan, C.K. Shim, S.J. Chung, S. Chong, D.D. Kim, A novel dermatology, Arch. Dermatol. Res. 303 (2011) 533–550, https://doi.org/
vesicular carrier, transethosome, for enhanced skin delivery of voriconazole: 10.1007/S00403-011-1163-7.
characterization and in vitro/in vivo evaluation, Colloids Surf. B Biointerfaces 92 [142] A. Kumari, S.K. Yadav, S.C. Yadav, Biodegradable polymeric nanoparticles based
(2012) 299–304, https://doi.org/10.1016/J.COLSURFB.2011.12.004. drug delivery systems, Colloids Surf. B Biointerfaces 75 (2010) 1–18, https://doi.
[120] V.P. Chavda, D. Vihol, B. Mehta, D. Shah, M. Patel, L.K. Vora, M. Pereira-Silva, A. org/10.1016/J.COLSURFB.2009.09.001.
C. Paiva-Santos, Phytochemical-loaded liposomes for anticancer therapy: an [143] P. Perugini, S. Simeoni, S. Scalia, I. Genta, T. Modena, B. Conti, F. Pavanetto,
updated review, Nanomedicine 17 (2022) 547–568, https://doi.org/10.2217/ Effect of nanoparticle encapsulation on the photostability of the sunscreen agent,
nnm-2021-0463. 2-ethylhexyl-p-methoxycinnamate, Int. J. Pharm. 246 (2002) 37–45, https://doi.
[121] S. Demartis, Q.K. Anjani, F. Volpe-Zanutto, A.J. Paredes, S.A. Jahan, L.K. Vora, R. org/10.1016/S0378-5173(02)00356-3.
F. Donnelly, E. Gavini, Trilayer dissolving polymeric microneedle array loading [144] J. Li, Y. Qiao, Z. Wu, Nanosystem trends in drug delivery using quality-by-design
Rose Bengal transfersomes as a novel adjuvant in early-stage cutaneous concept, J. Contr. Release 256 (2017) 9–18, https://doi.org/10.1016/J.
JCONREL.2017.04.019.
25
[145] P. Severino, G.G.G. de Oliveira, H.G. Ferraz, E.B. Souto, M.H.A. Santana, 407–419. https://www.researchgate.net/publication/236623203_Nanocrystals_
Preparation of gastro-resistant pellets containing chitosan microspheres for Current_Strategies_and_Trends. (Accessed 10 November 2022).
improvement of oral didanosine bioavailability, J Pharm Anal 2 (2012) 188–192, [168] X. Zhai, J. Lademann, C.M. Keck, R.H. Müller, Nanocrystals of medium soluble
https://doi.org/10.1016/J.JPHA.2012.02.005. actives—novel concept for improved dermal delivery and production strategy,
[146] F.R.S. Machado, D.F. Reis, D.L. Boschetto, J.F.M. Burkert, S.R.S. Ferreira, J. Int. J. Pharm. 470 (2014) 141–150, https://doi.org/10.1016/J.
V. Oliveira, C.A.v. Burkert, Encapsulation of astaxanthin from Haematococcus IJPHARM.2014.04.060.
pluvialis in PHBV by means of SEDS technique using supercritical CO2, Ind. Crop. [169] R. Shegokar, R.H. Müller, Nanocrystals: industrially feasible multifunctional
Prod. 54 (2014) 17–21, https://doi.org/10.1016/J.INDCROP.2014.01.007. formulation technology for poorly soluble actives, Int. J. Pharm. 399 (2010)
[147] R.H. Staff, K. Landfester, D. Crespy, Recent Advances in the Emulsion Solvent 129–139, https://doi.org/10.1016/J.IJPHARM.2010.07.044.
Evaporation Technique for the Preparation of Nanoparticles and Nanocapsules, [170] R. Peterson, Nanocrystals for use in topical cosmetic formulations and method of
Hierarchical Macromolecular Structures: 60 Years after the Staudinger Nobel production thereof - google Patents, US9 114 (2015), 077B2. https://patents.goo
Prize II, 2013, pp. 329–344. gle.com/patent/US9114077B2/en. (Accessed 11 November 2022).
[148] M.B. Oliveira, W. Song, L. Martín, S.M. Oliveira, S.G. Caridade, M. Alonso, J. [171] C.A. De Oliveira, D.D.A. Peres, F. Graziola, N.A.B. Chacra, G.L.B. De Araújo, A.
C. Rodríguez-Cabello, J.F. Mano, Development of an injectable system based on C. Flórido, J. Mota, C. Rosado, M.V.R. Velasco, L.M. Rodrigues, A.S. Fernandes, A.
elastin-like recombinamer particles for tissue engineering applications, Soft R. Baby, Cutaneous biocompatible rutin-loaded gelatin-based nanoparticles
Matter 7 (2011) 6426–6434, https://doi.org/10.1039/C0SM01302A. increase the SPF of the association of UVA and UVB filters, Eur. J. Pharmaceut.
[149] R. Alvarez-Román, A. Naik, Y.N. Kalia, R.H. Guy, H. Fessi, Enhancement of topical Sci. 81 (2016) 1–9, https://doi.org/10.1016/J.EJPS.2015.09.016.
delivery from biodegradable nanoparticles, Pharmaceut. Res. 21 (2004) [172] P. Kullavanijaya, H.W. Lim, Photoprotection, J Am Acad Dermatol. 52 (2005)
1818–1825, https://doi.org/10.1023/B:PHAM.0000045235.86197. EF. 937–958, https://doi.org/10.1016/j.jaad.2004.07.063.
[150] T.K. Dash, V.B. Konkimalla, Poly-ε-caprolactone based formulations for drug [173] M. Sohn, A. Hêche, B. Herzog, G. Imanidis, Film thickness frequency distribution
delivery and tissue engineering: a review, J. Contr. Release 158 (2012) 15–33, of different vehicles determines sunscreen efficacy, J. Biomed. Opt. 19 (2014),
https://doi.org/10.1016/j.jconrel.2011.09.064. 115005, https://doi.org/10.1117/1.JBO.19.11.115005.
[151] L. Vora, M. Tyagi, K. Patel, S. Gupta, P. Vavia, Self-assembled nanocomplexes of [174] C. Couteau, A. Demé, C. Cheignon, L.J.M. Coiffard, Influence of the hydrophilic-
anionic pullulan and polyallylamine for DNA and pH-sensitive intracellular drug lipophilic balance of sunscreen emulsions on their water resistance property, Drug
delivery, J. Nanopart. Res. 16 (2014) 2781, https://doi.org/10.1007/s11051- Dev. Ind. Pharm. 38 (2012) 1405–1407, https://doi.org/10.3109/
014-2781-8. 03639045.2011.653362.
[152] K.M. El-Say, H.S. El-Sawy, Polymeric nanoparticles: promising platform for drug [175] H. Li, S. Colantonio, A. Dawson, X. Lin, J. Beecker, Sunscreen application, safety,
delivery, Int. J. Pharm. 528 (2017) 675–691, https://doi.org/10.1016/J. and sun protection: the evidence, J. Cutan. Med. Surg. 23 (2019) 357–369,
IJPHARM.2017.06.052. https://doi.org/10.1177/1203475419856611.
[153] L.A. Frank, R.v. Contri, R.C.R. Beck, A.R. Pohlmann, S.S. Guterres, Improving [176] S. Pillai, C. Oresajo, J. Hayward, Ultraviolet radiation and skin aging: roles of
drug biological effects by encapsulation into polymeric nanocapsules, Wiley reactive oxygen species, inflammation and protease activation, and strategies for
Interdiscip Rev Nanomed Nanobiotechnol 7 (2015) 623–639, https://doi.org/ prevention of inflammation-induced matrix degradation - a review, Int. J.
10.1002/WNAN.1334. Cosmet. Sci. 27 (2005) 17–34, https://doi.org/10.1111/J.1467-
[154] M.M. Jiménez, J. Pelletier, M.F. Bobin, M.C. Martini, Influence of encapsulation 2494.2004.00241.X.
on the in vitro percutaneous absorption of octyl methoxycinnamate, Int. J. Pharm. [177] S.J. Balk, K.G. O’Connor, M. Saraiya, Counseling parents and children on sun
272 (2004) 45–55, https://doi.org/10.1016/J.IJPHARM.2003.11.029. protection: a national survey of pediatricians, Pediatrics 114 (2004) 1056–1064,
[155] R. Alvarez-Román, G. Barré, R.H. Guya, H. Fessi, Biodegradable polymer https://doi.org/10.1542/PEDS.2004-1305.
nanocapsules containing a sunscreen agent: preparation and photoprotection, [178] T. Teramura, M. Mizuno, H. Asano, N. Naito, K. Arakane, Y. Miyachi, Relationship
Eur. J. Pharm. Biopharm. 52 (2001) 191–195, https://doi.org/10.1016/S0939- between sun-protection factor and application thickness in high-performance
6411(01)00188-6. sunscreen: double application of sunscreen is recommended, Clin. Exp. Dermatol.
[156] M. Bhia, M. Motallebi, B. Abadi, A. Zarepour, M. Pereira-Silva, F. Saremnejad, A. 37 (2012) 904–908, https://doi.org/10.1111/J.1365-2230.2012.04388.X.
C. Santos, A. Zarrabi, A. Melero, S.M. Jafari, M. Shakibaei, Naringenin nano- [179] How to apply sunscreen, American Academy of Dermatology Association. (n.d.).
delivery systems and their therapeutic applications, Pharmaceutics 13 (2021) https://www.aad.org/public/everyday-care/sun-protection/shade-clothing-sun
291, https://doi.org/10.3390/PHARMACEUTICS13020291. screen/how-to-apply-sunscreen (accessed January 3, 2023).
[157] Y. Deng, A. Ediriwickrema, F. Yang, J. Lewis, M. Girardi, W.M. Saltzman, [180] W. Chen, M. He, L. Xie, L. Li, The optimal cleansing method for the removal of
A sunblock based on bioadhesive nanoparticles, Nat. Mater. 14 (2015) sunscreen:Water, cleanser or cleansing oil? J. Cosmet. Dermatol. 19 (2020)
1278–1285, https://doi.org/10.1038/nmat4422. 180–184, https://doi.org/10.1111/JOCD.12995.
[158] F. Tang, L. Li, D. Chen, Mesoporous silica nanoparticles: synthesis, [181] R.P. Stokes, B.L. Diffey, The water resistance of sunscreen and day-care products,
biocompatibility and drug delivery, Adv. Mater. 24 (2012) 1504–1534, https:// Br. J. Dermatol. 140 (1999) 259–263, https://doi.org/10.1046/J.1365-
doi.org/10.1002/ADMA.201104763. 2133.1999.02659.X.
[159] S.H. Wu, H.P. Lin, Synthesis of mesoporous silica nanoparticles, Chem. Soc. Rev. [182] L.L. Guan, H.W. Lim, T.F. Mohammad, Sunscreens and photoaging: a review of
42 (2013) 3862–3875, https://doi.org/10.1039/C3CS35405A. current literature, Am. J. Clin. Dermatol. 22 (2021) 819–828, https://doi.org/
[160] S.H. Tolbert, P.D. McFadden, D.A. Loy, New hybrid organic/inorganic 10.1007/S40257-021-00632-5.
polysilsesquioxane–silica particles as sunscreens, ACS Appl. Mater. Interfaces 8 [183] T.B. Fitzpatrick, The validity and practicality of sun-reactive skin types I through
(2016) 3160–3174. VI, Arch. Dermatol. 124 (1988) 869–871, https://doi.org/10.1001/
[161] G. Zaccariello, M. Back, M. Zanello, P. Canton, E. Cattaruzza, P. Riello, ARCHDERM.124.6.869.
A. Alimonti, A. Benedetti, Formation and controlled growth of bismuth titanate [184] A. Chardon, I. Cretois, C. Hourseau, Skin colour typology and suntanning
phases into mesoporous silica nanoparticles: an efficient self-sealing nanosystem pathways, Int. J. Cosmet. Sci. 13 (1991) 191–208, https://doi.org/10.1111/
for UV filtering in cosmetic formulation, ACS Appl. Mater. Interfaces 9 (2017) J.1467-2494.1991.TB00561.X.
1913–1921, https://doi.org/10.1021/ACSAMI.6B13252/SUPPL_FILE/ [185] S. del Bino, C. Duval, F. Bernerd, Clinical and biological characterization of skin
AM6B13252_SI_001.PDF. pigmentation diversity and its consequences on UV impact, Int. J. Mol. Sci. 19
[162] V. Ambrogi, L. Latterini, F. Marmottini, C. Pagano, M. Ricci, Mesoporous silicate (2018), https://doi.org/10.3390/IJMS19092668.
MCM-41 as a particulate carrier for octyl methoxycinnamate: sunscreen release [186] Y. Miyamura, S.G. Coelho, R. Wolber, S.A. Miller, K. Wakamatsu, B.Z. Zmudzka,
and photostability, J. Pharmaceut. Sci. 102 (2013) 1468–1475, https://doi.org/ S. Ito, C. Smuda, T. Passeron, W. Choi, J. Batzer, Y. Yamaguchi, J.Z. Beer, V.
10.1002/JPS.23478. J. Hearing, Regulation of human skin pigmentation and responses to ultraviolet
[163] A.L.M. Daneluti, F.M. Neto, N. Ruscinc, I. Lopes, M.V. Robles Velasco, J. Do radiation, Pigm. Cell Res. 20 (2007) 2–13, https://doi.org/10.1111/J.1600-
Rosário Matos, A.R. Baby, Y.N. Kalia, Using ordered mesoporous silica SBA-15 to 0749.2006.00358.X.
limit cutaneous penetration and transdermal permeation of organic UV filters, Int. [187] B.H. Mahmoud, E. Ruvolo, C.L. Hexsel, Y. Liu, M.R. Owen, N. Kollias, H.W. Lim, I.
J. Pharm. 570 (2019), 118633, https://doi.org/10.1016/J. H. Hamzavi, Impact of long-wavelength UVA and visible light on
IJPHARM.2019.118633. melanocompetent skin, J. Invest. Dermatol. 130 (2010) 2092–2097, https://doi.
[164] A.L.M. Daneluti, L.O. Guerra, M.V.R. Velasco, J. do Rosário Matos, A.R. Baby, Y. org/10.1038/JID.2010.95.
N. Kalia, Preclinical and clinical studies to evaluate cutaneous biodistribution, [188] L. Duteil, N. Cardot-Leccia, C. Queille-Roussel, Y. Maubert, Y. Harmelin,
safety and efficacy of UV filters encapsulated in mesoporous silica SBA-15, Eur. J. F. Boukari, D. Ambrosetti, J.P. Lacour, T. Passeron, Differences in visible light-
Pharm. Biopharm. 169 (2021) 113–124, https://doi.org/10.1016/J. induced pigmentation according to wavelengths: a clinical and histological study
EJPB.2021.10.002. in comparison with UVB exposure, Pigment Cell Melanoma Res 27 (2014)
[165] P. Da, S. Marcelino, R. Miliani Martinez, A. Luís, M. Daneluti, A. Lucía Morocho- 822–826, https://doi.org/10.1111/PCMR.12273.
Jácome, F. Vieira, L. Solino Pessoa, P. Rijo, C. Rosado, M.V. Robles Velasco, [189] I. Kohli, S. Chaowattanapanit, T.F. Mohammad, C.L. Nicholson, S. Fatima,
A. Rolim Baby, In vitro photoprotection and functional photostability of G. Jacobsen, N. Kollias, H.W. Lim, I.H. Hamzavi, Synergistic effects of long-
sunscreen lipsticks containing inorganic active compounds, Cosmetics 10 (2023) wavelength ultraviolet A1 and visible light on pigmentation and erythema, Br. J.
46, https://doi.org/10.3390/COSMETICS10020046. Dermatol. 178 (2018) 1173–1180, https://doi.org/10.1111/BJD.15940.
[166] R.H. Müller, R. Shegokar, S. Gohla, C.M. Keck, Nanocrystals: production, cellular [190] D. Moyal, Need for a well-balanced sunscreen to protect human skin from both
drug delivery, current and future products, in: Intracellular Delivery, Springer, Ultraviolet A and Ultraviolet B damage, Indian J. Dermatol. Venereol. Leprol. 78
Dordrecht, 2011, pp. 411–432, https://doi.org/10.1007/978-94-007-1248-5_15. (Suppl 1) (2012) 24–30, https://doi.org/10.4103/0378-6323.97352.
[167] S. Bansal, R. Kumria, Nanocrystals: current strategies and trends, International [191] T. Passeron, H.W. Lim, C.L. Goh, H.Y. Kang, F. Ly, A. Morita, J. Ocampo Candiani,
Journal of Research in Pharmaceutical and Biomedical Sciences 3 (2012) S. Puig, S. Schalka, L. Wei, B. Dréno, J. Krutmann, Photoprotection according to
skin phototype and dermatoses: practical recommendations from an expert panel,
26
J. Eur. Acad. Dermatol. Venereol. 35 (2021) 1460–1469, https://doi.org/ in vitro test method, Int. J. Cosmet. Sci. 29 (2007) 451–460, https://doi.org/
10.1111/JDV.17242. 10.1111/J.1468-2494.2007.00407.X.
[192] S. Shanbhag, A. Nayak, R. Narayan, U.Y. Nayak, Anti-aging and sunscreens: [219] A. Dimitrovska Cvetkovska, S. Manfredini, P. Ziosi, S. Molesini, V. Dissette,
paradigm shift in cosmetics, Adv. Pharmaceut. Bull. 9 (2019) 348–359, https:// I. Magri, C. Scapoli, A. Carrieri, E. Durini, S. Vertuani, Factors affecting SPF in
doi.org/10.15171/apb.2019.042. vitro measurement and correlation with in vivo results, Int. J. Cosmet. Sci. 39
[193] G. Jenkins, Molecular mechanisms of skin ageing, Mech. Ageing Dev. 123 (2002) (2017) 310–319, https://doi.org/10.1111/ICS.12377.
801–810, https://doi.org/10.1016/S0047-6374(01)00425-0. [220] S.Q. Wang, U. Osterwalder, K. Jung, Ex vivo evaluation of radical sun protection
[194] Sunscreen FAQs, American Academy of Dermatology Association. (n.d.). htt factor in popular sunscreens with antioxidants, J. Am. Acad. Dermatol. 65 (2011)
ps://www.aad.org/media/stats-sunscreen (accessed January 3, 2023). 525–530, https://doi.org/10.1016/J.JAAD.2010.07.009.
[195] K. Boch, E.A. Langan, K. Kridin, D. Zillikens, R.J. Ludwig, K. Bieber, Lichen [221] A. Crovara Pescia, P. Astolfi, C. Puglia, F. Bonina, R. Perrotta, B. Herzog,
planus, Front. Med. 8 (2021) 2089, https://doi.org/10.3389/ E. Damiani, On the assessment of photostability of sunscreens exposed to UVA
FMED.2021.737813/BIBTEX. irradiation: from glass plates to pig/human skin, which is best? Int. J. Pharm. 427
[196] E. Scheuer, E. Warshaw, Sunscreen allergy: a review of epidemiology, clinical (2012) 217–223, https://doi.org/10.1016/J.IJPHARM.2012.02.001.
characteristics, and responsible allergens, Dermatitis 17 (2006) 3–11, https://doi. [222] J. Aguilar Diaz De Leon, C.R. Borges, Evaluation of oxidative stress in biological
org/10.2310/6620.2006.05017. samples using the thiobarbituric acid reactive substances assay, J. Vis. Exp. 2020
[197] E. Mahé, A. Beauchet, M.F. de Maleissye, P. Saiag, Are sunscreens luxury (2020), https://doi.org/10.3791/61122.
products? J. Am. Acad. Dermatol. 65 (2011) https://doi.org/10.1016/j. [223] R. Sauce, , C.A.S. de O. Pinto, C. Ayala-Jara, Z.A. Prieto, M.V.R. Velasco, A.
jaad.2010.06.043. R. Baby, Preliminary protocol development of a HPLC-TBARS-EVSC (ex vivo
[198] S. Xu, M. Kwa, A. Agarwal, A. Rademaker, R.v. Kundu, Sunscreen product stratum corneum) assay for skin research: application in a sunscreen system, Sci.
performance and other determinants of consumer preferences, JAMA Dermatol Pharm. 89 (2021) 17, https://doi.org/10.3390/SCIPHARM89020017.
152 (2016) 920–927, https://doi.org/10.1001/jamadermatol.2016.2344. [224] S.H. Lee, New Technical Developments in Sun Care and Blue Light Defense,
[199] D. Moyal, V. Alard, C. Bertin, F. Boyer, M.W. Brown, L. Kolbe, P. Matts, SUNJIN Beauty Science: Gyeonggi-do, Korea, 2018, p. 134.
M. Pissavini, The revised COLIPA in vitro UVA method, Int. J. Cosmet. Sci. 35 [225] Y. Kuse, K. Ogawa, K. Tsuruma, M. Shimazawa, H. Hara, Damage of
(2013) 35–40, https://doi.org/10.1111/J.1468-2494.2012.00748.X. photoreceptor-derived cells in culture induced by light emitting diode-derived
[200] S.Q. Wang, J.W. Stanfield, U. Osterwalder, In vitro assessments of UVA protection blue light, Sci. Rep. 4 (2014) 1–12.
by popular sunscreens available in the United States, J. Am. Acad. Dermatol. 59 [226] J.R. Mark, F. Gelpi-Hammerschmidt, E.J. Trabulsi, L.G. Gomella, Blue light
(2008) 934–942, https://doi.org/10.1016/J.JAAD.2008.07.043. cystoscopy for detection and treatment of non-muscle invasive bladder cancer,
[201] S. Fuehring, Standardisation Mandate Assigned to CEN Concerning Methods for Can. J. Urol. 19 (2012) 6227–6231.
Testing Efficacy of Sunscreen Products, European Commission, Brussels, Belgium, [227] S.B. Brown, E.A. Brown, I. Walker, The present and future role of photodynamic
2006. therapy in cancer treatment, Lancet Oncol. 5 (2004) 497–508, https://doi.org/
[202] K. Hedayat, S. Ahmad Nasrollahi, A. Firooz, Quick and brief review: comparison 10.1016/S1470-2045(04)01529-3.
between different in vivo SPF determination methods, J. Cosmet. Dermatol. 18 [228] T.J. Century, I.R. Fenichel, S.B. Horowitz, J. Century, T.J. Horowitz, , J.,
(2019) 1617–1623, https://doi.org/10.1111/JOCD.12941. H. Orowitz, S.B. Fenichel, , J. G’n. Physiol, M. Frank, P.L. Paine, C.M. Feldherr, L.
[203] W. Zou, R. Ramanathan, S. Urban, C. Sinclair, K. King, R. Tinker, V. Bansal, C. Moore, , S.B. Ho Row It Z, P.L.W.R. Paine, Y. Kanno, C. Legname, L. Goldstein,
Sunscreen testing: a critical perspective and future roadmap, TrAC, Trends Anal. A.S. Mcfarlane, M.B. Macfarlane, C.P. Anties, G.H. Eagles, Retinal sensitivity to
Chem. 157 (2022), https://doi.org/10.1016/j.trac.2022.116724. damage from short wavelength light, Nature 260 (1976) 153–155, https://doi.
[204] ISO - ISO/CD 23698 - Cosmetics Sun protection test methods- Measurement of the org/10.1038/260153a0.
Sunscreen Efficacy by Diffuse Reflectance Spectroscopy (n.d.), https://www.iso. [229] N. Mistry, Guidelines for formulating anti-pollution products, Cosmetics 4 (2017)
org/standard/76699.html. (Accessed 8 November 2022). 57, https://doi.org/10.3390/COSMETICS4040057.
[205] C. Cole, J. Silverman, M. Bonitatibus, Evaluating sunscreen ultraviolet protection [230] M. Megna, S. Lembo, N. Balato, G. Monfrecola, “ Active” photoprotection:
using a polychromatic diffuse reflectance device, Photodermatol. Photoimmunol. sunscreens with DNA repair enzymes, G. Ital. Dermatol. Venereol. 152 (2017)
Photomed. 35 (2019) 436–441, https://doi.org/10.1111/PHPP.12496. 302–307.
[206] M. Rohr, N. Ernst, A. Schrader, Hybrid diffuse reflectance spectroscopy: non- [231] A. Rosenthal, M. Stoddard, L. Chipps, J. Herrmann, Skin cancer prevention: a
erythemal in vivo testing of sun protection factor, Skin Pharmacol. Physiol. 31 review of current topical options complementary to sunscreens, J. Eur. Acad.
(2018) 220–228, https://doi.org/10.1159/000488249. Dermatol. Venereol. 33 (2019) 1261–1267, https://doi.org/10.1111/JDV.15522.
[207] DSM SUNSCREEN OPTIMIZERTM. https://www.sunscreen-optimizer.com/index. [232] S. Singer, S. Karrer, M. Berneburg, Modern sun protection, Curr. Opin. Pharmacol.
html. (Accessed 8 November 2022). 46 (2019) 24–28, https://doi.org/10.1016/J.COPH.2018.12.006.
[208] Sunscreen Simulator. https://sunscreensimulator.basf.com/Sunscreen_Simulator [233] E. Emanuele, V. Altabas, K. Altabas, E. Berardesca, Topical application of
/login. (Accessed 8 November 2022). preparations containing DNA repair enzymes prevents ultraviolet-induced
[209] Y.J. Hwang, H.J. Park, H.J. Hahn, J.Y. Kim, J.H. Ko, Y.W. Lee, Y.B. Choe, K. telomere shortening and c-FOS proto-oncogene hyperexpression in human skin:
J. Ahn, Immediate pigment darkening and persistent pigment darkening as means an experimental pilot study, J. Drugs Dermatol. JDD 12 (2013) 1017–1021. http
of measuring the ultraviolet A protection factor in vivo: a comparative study, Br. s://europepmc.org/article/med/24002149. (Accessed 10 November 2022).
J. Dermatol. 164 (2011) 1356–1361, https://doi.org/10.1111/J.1365- [234] M. Carducci, P.S. Pavone, G. de Marco, S. Lovati, V. Altabas, K. Altabas,
2133.2011.10225.X. E. Emanuele, Comparative effects of sunscreens alone vs sunscreens plus DNA
[210] M.S. Latha, J. Martis, V. Shobha, R.S. Shinde, S. Bangera, B. Krishnankutty, repair enzymes in patients with Actinic keratosis: clinical and molecular findings
S. Bellary, S. Varughese, P. Rao, B.R.N. Kumar, Sunscreening agents: a review, from a 6-month, randomized, clinical study, J. Drugs Dermatol. JDD 14 (2015)
J Clin Aesthet Dermatol 6 (2013) 26. /pmc/articles/PMC3543289/. (Accessed 10 986–990. https://europepmc.org/article/med/26355618. (Accessed 10
November 2022). November 2022).
[211] C. Routaboul, A. Denis, A. Vinche, Immediate pigment darkening: description, [235] D. Barolet, F. Christiaens, M.R. Hamblin, Infrared and skin: friend or foe,
kinetic and biological function, Eur. J. Dermatol. 9 (1999) 95–99. https://www. J. Photochem. Photobiol., B 155 (2016) 78–85, https://doi.org/10.1016/J.
jle.com/fr/revues/ejd/e-docs/immediate_pigment_darkening_description_kinet JPHOTOBIOL.2015.12.014.
ic_and_biological_function_100373/article.phtml?tab=texte. (Accessed 10 [236] S.M. Schieke, P. Schroeder, J. Krutmann, Cutaneous effects of infrared radiation:
November 2022). from clinical observations to molecular response mechanisms, Photodermatol.
[212] FDA Guidelines 2021 on In-Vitro Testing of Sunscreen Formulations (n.d.), https Photoimmunol. Photomed. 19 (2003) 228–234, https://doi.org/10.1034/J.1600-
://www.fda.gov/regulatory-information/search-fda-guidance-documents/in-vit 0781.2003.00054.X.
ro-permeation-test-studies-topical-drug-products-submitted-andas (Accessed on 2 [237] S.J. Kim, J. Bae, S.E. Lee, J.B. Lee, C.H. Park, D.H. Lim, M.S. Park, J. Ha, A novel
march, 2023). in vivo test method for evaluating the infrared radiation protection provided by
[213] ISO 24443:2021(en), Cosmetics — Determination of sunscreen UVA sunscreen products, Skin Res. Technol. 25 (2019) 890–895, https://doi.org/
photoprotection in vitro (n.d.), https://www.iso.org/obp/ui/#iso:std:iso:24443: 10.1111/SRT.12754.
ed-2:v2:en. (Accessed 8 November 2022). [238] L.T.N. Ngoc, V. van Tran, J.Y. Moon, M. Chae, D. Park, Y.C. Lee, Recent trends of
[214] H. Bendová, J. Akrman, A. Krejčí, L. Kubáč, D. Jírová, K. Kejlová, H. Kolářová, sunscreen cosmetic: an update review, Cosmetics 6 (2019), https://doi.org/
M. Brabec, M. Malý, In vitro approaches to evaluation of Sun Protection Factor, 10.3390/COSMETICS6040064.
Toxicol. Vitro 21 (2007) 1268–1275, https://doi.org/10.1016/j.tiv.2007.08.022. [239] B. Nieuwenhujisen, Composition of a water-soluble sunscreen preparation for
[215] Cosmetics Europe: Guidelines For Evaluating Sun Product Water Resistance, in: , acne rosacea, US8 337 (2012) 820B2. https://patents.google.com/patent/US833
2005. https://www.cosmeticseurope.eu/files/7914/6407/7400/Guidelines_for_E 7820B2/en. (Accessed 11 November 2022).
valuating_Sun_Product_Water_Resistance_-_2005.pdf (Acessed on 2 March, 2023). [240] A. Kerr, J. Ferguson, Photoallergic contact dermatitis, Photodermatol.
[216] ISO 16217:2020(en), Cosmetics — Sun protection test methods — Water Photoimmunol. Photomed. 26 (2010) 56–65, https://doi.org/10.1111/J.1600-
immersion procedure for determining water resistance, (n.d.). https://www.iso. 0781.2010.00494.X.
org/obp/ui/#iso:std:iso:16217:ed-1:v1:en (accessed November 8, 2022). [241] A. Faurschou, D.M. Beyer, A. Schmedes, M.K. Bogh, P.A. Philipsen, H.C. Wulf, The
[217] ISO 18861:2020(en), Cosmetics — Sun protection test methods — Percentage of relation between sunscreen layer thickness and vitamin D production after
water resistance, (n.d.). https://www.iso.org/obp/ui/#iso:std:iso:18861:ed-1:v1: ultraviolet B exposure: a randomized clinical trial, Br. J. Dermatol. 167 (2012)
en (accessed November 8, 2022). 391–395, https://doi.org/10.1111/J.1365-2133.2012.11004.X.
[218] M. Pissavini, V. Alard, U. Heinrich, K. Jenni, V. Perier, V. Tournier, D. Lutz, [242] E.D. Gorham, S.B. Mohr, C.F. Garland, G. Chaplin, F.C. Garland, Do sunscreens
M. Meloni, D. Kockott, L. Ferrero, B. Gonzalez, L. Zastrow, H. Tronnier, In vitro increase risk of melanoma in populations residing at higher latitudes? Ann.
assessment of water resistance of sun care products: a reproducible and optimized Epidemiol. 17 (2007) 956–963.
27
[243] P. Autier, Sunscreen abuse for intentional sun exposure, Br. J. Dermatol. 161 [254] M. Pelizzo, E. Zattra, P. Nicolosi, A. Peserico, D. Garoli, M. Alaibac, In vitro
(2009) 40–45, https://doi.org/10.1111/J.1365-2133.2009.09448.X. evaluation of sunscreens: an update for the clinicians, ISRN Dermatol 2012
[244] D.R. Sambandan, D. Ratner, Sunscreens: an Overview and Update, JAM ACAD, (2012) 1–4, https://doi.org/10.5402/2012/352135.
2011. [255] J.A. Ruszkiewicz, A. Pinkas, B. Ferrer, T.v. Peres, A. Tsatsakis, M. Aschner,
[245] J. Wu, W. Liu, C. Xue, S. Zhou, F. Lan, L. Bi, H. Xu, X. Yang, F.D. Zeng, Toxicity Neurotoxic effect of active ingredients in sunscreen products, a contemporary
and penetration of TiO2 nanoparticles in hairless mice and porcine skin after review, Toxicol Rep 4 (2017) 245–259, https://doi.org/10.1016/J.
subchronic dermal exposure, Toxicol. Lett. 191 (2009) 1–8, https://doi.org/ TOXREP.2017.05.006.
10.1016/J.TOXLET.2009.05.020. [256] About sunscreen regulation | Therapeutic Goods Administration (TGA), (n.d.).
[246] P. Filipe, J.N. Silva, R. Silva, J.L. Cirne De Castro, M. Marques Gomes, L.C. Alves, https://www.tga.gov.au/resources/resource/guidance/about-sunscreen-regu
R. Santus, T. Pinheiro, Stratum corneum is an effective barrier to TiO2 and ZnO lation (accessed October 20, 2022).
nanoparticle percutaneous absorption, Skin Pharmacol. Physiol. 22 (2009) [257] O.P. Egambaram, S. Kesavan Pillai, S.S. Ray, Materials science challenges in skin
266–275, https://doi.org/10.1159/000235554. UV protection: a review, Photochem. Photobiol. 96 (2020) 779–797, https://doi.
[247] R. Marks, P.A. Foley, D. Jolley, K.R. Knight, J. Harrison, S.C. Thompson, The org/10.1111/php.13208.
effect of regular sunscreen use on vitamin D levels in an Australian population: [258] V.P. Chavda, Chapter 4 - Nanobased Nano Drug Delivery: A Comprehensive
results of a randomized controlled trial, JAMA Dermatol 131 (1995) 415–421, Review, in: S.S. Mohapatra, S. Ranjan, N. Dasgupta, R.K. Mishra, S.B.T.-A. of T.N.
https://doi.org/10.1001/ARCHDERM.1995.01690160043006. D., D.S. Thomas (Eds.), Micro and Nano Technologies, Elsevier, 2019, pp. 69–92.
[248] M.F. Holick, Vitamin D: a millennium perspective, J. Cell. Biochem. 88 (2003) [259] V.P. Chavda, Chapter 1 - Nanotherapeutics and Nanobiotechnology, in: S.
296–307, https://doi.org/10.1002/JCB.10338. S. Mohapatra, S. Ranjan, N. Dasgupta, R.K. Mishra, S. Thomas (Eds.), Applications
[249] L. Mu, R.L. Sprando, Application of nanotechnology in cosmetics, Pharm. Res. (N. of Targeted Nano Drugs and Delivery Systems, Elsevier, 2019, pp. 1–13.
Y.) 27 (2010) 1746–1749, https://doi.org/10.1007/S11095-010-0139-1. https://doi.org/10.1016/B978-0-12-814029-1.00001-6.
[250] FDA’s Approach to Regulation of Nanotechnology Products | FDA, (n.d.). http [260] V.P. Chavda, V.V. Sugandhi, C.V. Pardeshi, R.J. Patil, M. Joshi, B. Patel,
s://www.fda.gov/science-research/nanotechnology-programs-fda/fdas-approach A. Khadela, R. Bezbaruah, B. Bhattacharjee, P.C. Balar, L.K. Vora, Engineered
-regulation-nanotechnology-products (accessed October 18, 2022). exosomes for cancer theranostics: Next-generation tumor targeting, J. Drug Deliv.
[251] G.J. Nohynek, H. Schaefer, Benefit and risk of organic ultraviolet filters, Regul. Sci. Technol. 85 (2023), 104579. https://doi.org/10.1016/j.jddst.2023.104579.
Toxicol. Pharmacol. 33 (2001) 285–299, https://doi.org/10.1006/ [261] V.P. Chavda, A. Pandya, L. Kumar, N. Raval, L.K. Vora, S. Pulakkat, V. Patravale,
RTPH.2001.1476. Salwa, Y. Duo, B.Z. Tang, Exosome nanovesicles: a potential carrier for
[252] G. Pirotta, An overview of sunscreen regulations in the world, Househ. Personal therapeutic delivery, J. Nano Today. 49 (2023), 101771, https://doi.org/
Care Today 10 (2015). https://www.researchgate.net/profile/Giulio-Pirotta 10.1016/j.nantod.2023.101771.
-2/publication/283515177_An_overview_of_sunscreen_regulations_in_the_world/l [262] V.P. Chavda, D. Shah, Chapter 25 - Self-emulsifying delivery systems: one step
inks/563cdb7508aec6f17dd7e0d6/An-overview-of-sunscreen-regulations-in-th ahead in improving solubility of poorly soluble drugs, in: A. Ficai, A.M.B.T.-N. for
e-world.pdf. (Accessed 10 November 2022). C.T. Grumezescu (Eds.), Micro and Nano Technologies, Elsevier, 2017,
[253] J.W. Stanfield, H. Ou-Yang, T. Chen, C. Cole, Y. Appa, Multi-laboratory validation pp. 653–718. https://doi.org/10.1016/B978-0-323-46144-3.00025-8.
of very high sun protection factor values, Photodermatol. Photoimmunol. [263] V.P. Chavda, S. Dawre, A. Pandya, L.K. Vora, D.H. Modh, V. Shah, D.J. Dave,
Photomed. 27 (2011) 30–34. V. Patravale, Lyotropic liquid crystals for parenteral drug delivery, J. Control.
Release 349 (2022) 533–549, https://doi.org/10.1016/j.jconrel.2022.06.062.
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Journal of Drug Delivery Science and Technology 86 (2023) 104720

Contents lists available at ScienceDirect

Journal of Drug Delivery Science and Technology

Sunscreens: A comprehensive review with the application

Fig. 3. Various nanocarriers useful in sunscreen formulations.

4.2. Sunsphere 4.3. Transfersomes

One notable advantage of this nano-structure lipid carrier is its high

methods against UV rays helps the prevention of skin aging such as

Sunscreen has been proven effective in prevention of several diseases

Table 6 Table 6 (continued )

Table 7 9. Safety and regulatory aspects of sunscreen formulations

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