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Niosomal drug delivery for transdermal targeting:

recent advances

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Research and Reports in Transdermal Drug Delivery
29 July 2015
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Rita Muzzalupo Abstract: Niosomes are vesicular nanocarriers and are receiving much attention as potential
Lorena Tavano transdermal drug delivery systems due to properties such as enhanced drug penetration, local
Department of Pharmacy and Health
depot for sustained drug release, and a rate-limiting membrane for modulation of systemic
and Nutrition Science, University absorption of drugs via the skin. Several mechanisms have been proposed to explain the ability
of Calabria, Edificio Polifunzionale, of niosomes to increase drug transfer through the skin. Niosomal carriers are suitable for the
Cosenza, Italy
transdermal delivery of numerous pharmacological agents, including antioxidant, anticancer,
anti-inflammatory, antimicrobial, and antibacterial molecules, and this review attempts to provide
an exhaustive collection of recent investigations in this interesting field, with special emphasis
on the strategies used to enhance the potential of niosomes.
Keywords: niosomes, transdermal, permeation, enhancer, drug delivery

Introduction
This review provides a brief overview of issues related to niosomes by explaining
their chemical composition, structure, advantages, and applications, makes general
remarks on niosomes as percutaneous permeation enhancers, and discusses the find-
ings of investigations done over the past 5 years on niosomal drug delivery systems
for transdermal applications.
Niosomes are vesicular nanocarriers and have received much attention as poten-
tial drug delivery systems in the last 30 years due to their unique advantages. They
have lamellar (bilayer) structures composed of amphiphilic molecules surrounded
by an aqueous compartment. These amphiphilic molecules, known as surfactants,
contain both hydrophobic groups (tails) and hydrophilic groups (heads) and show
self-assembling properties, aggregating into a variety of shapes like micelles or into
a planar lamellar bilayer.1 Surfactants that could be used as potential drug delivery
systems include sorbitan esters and analogs, sugar-based, polyoxyethylene-based,
polyglycerol, or crown ether-based surfactants, sometimes in addition to membrane
additives, such as cholesterol or its derivatives. Nonionic surfactants are preferred
because they have less potential to cause irritation, which decreases in order of cationic
. anionic . nonionic.2
The unique structures of niosomes as vesicular systems make them capable of
Correspondence: Rita Muzzalupo
Dipartimento di Farmacia e Scienze della
encapsulating both hydrophilic and lipophilic substances. Hydrophilic drugs are usu-
Salute e della Nutrizione, Università della ally encapsulated in the inner aqueous core or adsorbed on the bilayer surfaces, while
Calabria, Edificio Polifunzionale, 87036
Arcavacata di Rende, Cosenza, Italy
lipophilic substances are entrapped by their partitioning into the lipophilic domain of
Email [email protected] the bilayers (Figure 1).

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• The physicochemical properties of niosomes, such as

their shape, fluidity, and size, can be easily controlled by
changing their structural composition and the method of
production
• Niosomes are able to encapsulate a large amount of mate-
rial in a small vesicular volume
• The structure of niosomes protect drug ingredients from
heterogeneous factors present both inside and outside the
body, so niosomes can be used for the delivery of labile
and sensitive drugs
Figure 1 Schematic representation of a niosomal vesicle.
• Niosomes improve the therapeutic performance of drug
molecules by delaying clearance from the circulation and
restricting effects to target cells
The formation of vesicular assemblies requires the input • Niosomes can be administered via different routes, such
of some form of energy, and all the experimental methods as oral, parenteral, and topical, and using different dos-
investigated involve hydration of a mixture of surfactants age forms such as powders, suspensions, and semisolids,
above the gel to liquid phase transition temperature of the improving the oral bioavailability of poorly soluble drugs
system, followed by optional size reduction to obtain a col- and also enhancing the permeability of drugs through the
loidal dispersion.3 Because of their potential ability to carry skin when applied topically
a variety of therapeutics, these vesicles have been widely • The aqueous vehicle-based suspension formulation
used as drug delivery systems to achieve drug targeting, results in better patient compliance when compared with
controlled release, and permeation enhancement.4 In fact, oily dosage forms; in addition, niosomal dispersion, being
niosomes can act as therapeutic reservoirs for delivery of aqueous, can be emulsified in a nonaqueous phase to
a drug in a controlled manner to enhance bioavailability, regulate the drug release rate
obtaining a therapeutic effect over a longer period of time, • Niosomes have been reported to achieve better patient
and can be modified by altering the composition, concen- adherence and satisfaction and also better effectiveness
tration of various additives, and surface charge of vesicle than conventional oily formulations.
components and membrane additives. 5 Moreover, drug At the same time, niosomes have some disadvantages,
ionization has been found to modulate the physicochemi- which may decrease their shelf life, and include physical
cal properties of the vesicles and their percutaneous per- and chemical instability, aggregation, fusion of vesicles, and
meation profiles.6 In recent decades, niosomes have been leaking or hydrolysis of the encapsulated drug. Moreover, the
investigated in-depth as potential carriers for sustained and methods required for preparation of multilamellar vesicles,
targeted drug delivery, since they are easily derivatized to such as extrusion or sonication, are time-consuming and may
enhance vesicles versatility to improve the affinity for the require specialized equipment for processing.9
target site.7
Niosomes versus liposomes
Advantages and disadvantages Niosomes and liposomes are functionally the same, with
of niosomal carriers similar physicochemical properties depending on the com-
Niosomes combine several advantages with respect to other position of the bilayer and the preparation methods used
nanocarriers:8 (Table 1). They act as amphiphilic vesicles, and both can be
• Surfactants used to prepare niosomes are biodegradable, used for targeted and sustained drug delivery.
biocompatible, and not immunogenic Several authors have reported that the function of nio-
• The method used for routine and large-scale produc- somes in vivo is similar to that of liposomes.10 Niosomal
tion of niosomes does not involve use of unacceptable and liposomal vesicular systems have similar applica-
solvents tions in the pharmaceutical and cosmetic field, but differ
• Due to the chemical stability of their structural compo- chemically in their structure units; niosomes are made of
sition, the handling and storage of niosomes does not surfactants whereas liposomes are based on phospholipids,
require any special conditions meaning that niosomes have greater stability and lack many

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Dovepress Niosomal drug delivery for transdermal targeting

Table 1 Niosomes versus liposomes: a summary action, including active, ­passive, and magnetic targeting,
Niosomes Liposomes leading to more advanced and specific macromolecular
Components Surfactants Phospholipids drug carriers.16
Component availability High Low
Component purity
Preparation and storage
Good
No special
Variable
Inert atmosphere and
Toxicity of niosomes
conditions required low temperature The toxicity of niosomes is related to their components, ie,
Stability Very good Low nonionic surfactants are more biocompatible and less toxic
Cost Low High than their anionic, amphoteric, and cationic counterparts.
When the same surfactants are in the form of vesicular
of the disadvantages associated with liposomes, ie, high systems, these properties strongly decrease. There is little
cost, low availability, and the variable purity problems research published on the toxicity of niosomes and the types
associated with phospholipids. Niosomes do not require of surfactant included.17 Hofland et al18 evaluated the toxic-
special conditions such as low temperature or an inert atmo- ity of the types of surfactant used in niosomal formulations
sphere during preparation and storage; these features make to human keratinocytes, and demonstrated that ester types
niosomes more attractive for industrial manufacturing.11 of surfactant are less toxic than ether types due to enzy-
On the other hand, niosomes offer several advantages over matic degradation of bonds in esters. Hemolytic tests are
liposomes, such as intrinsic skin penetration-enhancing traditionally used to predict the toxicity of a surfactant and
properties.12 in vesicular systems derived from them.19 Recently, it has
been demonstrated that the ability of niosomes to disrupt
Applications of niosomes erythrocytes depends on the length of the alkyl chain in
Niosomes were introduced for use in the cosmetic industry. the surfactant and on the size of the colloidal aggregates
The first report on surfactant vesicles came from the cos- in solution. Presumably, a shorter carbon chain intercalates
metic applications devised by L’Oreal.13 Phospholipids and better into the membranes of erythrocytes, destructing their
nonionic surfactant have been reported to act as penetration molecular organization; niosomes have more difficulty to
enhancers that can overcome the barrier of transdermal interact with biological membranes, resulting in substantial
drug delivery.14 Since then, there has been increasing inter- hemolysis.20 Niosomes prepared with bolaform surfactants
est in the use of niosomes in the pharmaceutical, cosmetic, showed encouraging safety and tolerability data both in vitro
and food industries, leading to the publication of more in human keratinocytes and in vivo in human volunteers,
than 1,200 research articles, about 200 patents, and six who showed no skin erythema when topically treated with a
clinical trials from 1980 onwards. Most of these publica- drug-free bolaform niosome formulation.21
tions make reference to the importance of characterization
of nanovectors. Niosomes as percutaneous
Niosomal carriers are suitable for the delivery of numer- permeation enhancers
ous pharmacological and diagnostic agents, including When applying niosomes to the skin, one has to differentiate
antioxidants, anticancer, anti-inflammatory, antiasthma, what type of effect is required, ie, a local effect within the
antimicrobial, anti-Alzheimer’s, and antibacterial mol- skin (dermal drug delivery) or a systemic effect accompanied
ecules, oligonucleotides, and others.5 Depending on the type by permeation through the skin (transdermal drug delivery),
of drug, surfactant, disease, and anatomical site involved, as shown in Figure 2.22
various routes of administration exist for niosomal drugs, Reaching the bloodstream is the aim of transdermal
ie, intravenous, intramuscular, oral, ocular, subcutaneous, targeting, and is becoming a focus of interest for many
pulmonary, and transdermal.4 Several other routes have pharmaceutical research groups studying diseases such as
been used to administer niosomal drugs, including the inflammation, cancer, psoriasis, alopecia, and acne.11 The
intraperitoneal and vaginal routes. Niosomes have been transdermal route has several advantages over the conven-
used for successful targeting of drugs to various organs tional routes of drug administration: peak and trough levels
like the liver and brain or to pathological districts such as in serum (a risk and inconvenience of intravenous therapy)
tumor, enhancing drugs pharmacological activities while are avoided; first-pass hepatic metabolism and gastrointes-
reducing side effects.15 In particular, targeted niosomal tinal degradation (pH, enzymatic activity, and interactions
systems have been designed with different mechanisms of with food, beverages, and other orally administered drugs),

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DDDS TDDS induced by their presence in a formulation, such as enhanced

drug penetration, local depot for sustained drug release and
Stratum corneum
a rate-limiting membrane for modulation of systemic drug
Epidermis
absorption via the skin.26
Dermis An important research contribution to evaluation of
niosomal vesicles as a permeation enhancer was made in
Capillary
vessel 2011. The objective of the researchers was to determine
Subcutaneous
tissue
if the increased hydrophilic drug permeation across the
Fatty tissue
skin, which is always observed with vesicular systems, is
Figure 2 Dermal drug delivery systems and transdermal drug delivery system. dependent on the structural organization of the niosomes
Abbreviations: DDDS, Dermal drug delivery systems; TDDS, transdermal drug that are used to transport the active molecule or if it is only
delivery systems.
dependent on the dual nature of surfactant.27 Percutaneous
permeation profiles of sulfadiazine were obtained by using
are avoided, leading to an increase in drug bioavailability surfactants both as components of niosomal systems and
and efficacy; and it can serve as an alternative to oral drug as submicellar solution, according to the following experi-
administration when that route is unsuitable (eg, vomiting and mental conditions: treatment with a niosome formulation,
diarrhea). Other advantages of the transdermal route include a submicellar solution of surfactant, aqueous drug solution
the accessibility of the skin, the relatively large surface area after pretreatment of the skin with empty niosomes, and
for absorption, and the fact that it is noninvasive, making the aqueous drug solution after pretreatment of the skin with
patient more compliant. a submicellar solution of surfactant. The results showed
However, the transdermal route of drug administration has that permeation of sulfadiazine was not increased after
a major disadvantage, ie, a low penetration rate through the pretreatment with a submicellar solution of surfactant or
skin. Only a limited number of drugs can be formulated as direct treatment with a submicellar solution of surfactant
transdermal delivery systems due to the effect of the stratum containing the drug respect to the control. Also, pretreatment
corneum, which serves as a rate limiting step during drug with empty niosomes followed by treatment with the drug
permeation. This layer is very selective with respect to the solution showed similar trends, meaning that only direct
types of molecule that it allows to be transported through the treatment of the skin with loaded niosomes increased the
skin; therefore, only molecules with specific physicochemical percutaneous permeation of the drug, confirming the role of
properties can cross the skin adequately.23 niosomes as enhancers. Direct contact between the vesicles
Drug transfer across the stratum corneum is mainly a and the skin is essential for efficient delivery, although
passive process and can occur via three routes: intercellular, surfactants apparently do not penetrate into the deeper skin
transcellular (paracellular), and transappendageal. Once it has layers, and the presence of drug and vesicular carriers must
traversed the epidermis, a compound may be removed by the be simultaneous. Only in this case the intercellular lipid bar-
dermal circulation or be transported to deeper tissues.24 Many rier in the stratum corneum would be dramatically changed
strategies have been assessed for their ability to overcome to be more permeable.
the barrier function of the stratum corneum and to improve
drug transport into the skin. In particular, penetration enhanc- Mechanisms of action of niosomes
ers may act by one or more of three potential mechanisms as permeation enhancers
according to the lipid-protein-partitioning theory: they can There is no single mechanism that can sufficiently explain
alter the intercellular lipid structure between the corneocytes the ability of niosomes to increase drug transfer through
to increase diffusivity; and they can modify intracellular the skin, and several mechanisms (Figure 3) have been
protein domains within the horny layer and may increase proposed, including: alteration of the barrier function of the
partitioning of the drug into the skin tissue.25 During the last stratum corneum, as a result of reversible perturbation of lipid
decade, niosomes have undergone intensive investigation for organization;28 reduction of transepidermal water loss, which
transdermal drug delivery, and seem to be promising vehicles increases hydration of the stratum corneum and loosens its
for active substances and targeting to the skin layer. Niosomes closely-packed cellular structure;29 and adsorption and/or
are becoming popular in the field of topical drug delivery fusion of niosomes on the surface of the skin, as revealed by
due to their outstanding characteristics and the properties freeze fracture electron microscopy and small angle X-ray

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Dovepress Niosomal drug delivery for transdermal targeting

Possible mechanisms of action of niosomes as skin drug Topical administration

delivery systems

Fusion with the

stratum corneum

Endocytosis

Figure 3 Mechanisms of action of niosomes as skin drug delivery systems.

scattering, leading to a high thermodynamic activity gradi- vehicle, which can be achieved by adding gelling agents
ent of drug at the interface, which is the driving force for to niosomal dispersions, thereby forming a niosomal gel.34
permeation of a drug.30 Niosomal gels were found to enhance retention of thera-
Adsorption of niosomes onto the cell surface occurs with peutics by the skin and to provide high and sustained drug
little or no internalization of either aqueous or lipid compo- concentrations in the skin.35 A further evolution of niosomes
nents; it may take place either as a result of attracting physical is represented by proniosomes or “dry niosomes”, which have
forces or as a result of binding by specific receptors to ligands been proposed as niosomal formulations; these need to be
on the vesicle membrane and transfer of drug directly from hydrated before use, and hydration results in formation of
vesicles to the skin. On the other hand, niosomes may fuse an aqueous niosomal dispersion. Proniosomes decrease the
with the cell membrane, resulting in complete mixing of the aggregation, leakage, and fusion problems associated with
niosomal contents with the cytoplasm. Finally, niosomes may traditional niosomes and offer a versatile transdermal drug
be engulfed by the cell (endocytosis), with lysozymes pres- delivery system because, upon application to the skin, they
ent in the cytoplasm degrading or digesting the membranous become hydrated with water from the skin under occlusion.36
structure of the niosome, thereby releasing the entrapped A summary of the findings of investigations over the past
material into the medium.31,32 5 years for transdermal niosomal drug delivery systems is
given in Table 2.
Recent advances in niosomal Niosomes containing nonsteroidal anti-inflammatory
formulations for transdermal drugs (NSAIDs) have been prepared by different groups of
drug targeting researchers. These drugs may cause local mucosal irritation
During recent years, transdermal drug delivery from nio- and undergo first-pass metabolism in the liver after oral
somes has been studied in a number of disease models, and administration, which leads to partial inactivation. Thus,
current efforts are focused on optimization of procedures, only 50% of the drug reaches the circulation. Topical dosage
new compositions, and final formulations. For example, new forms are desirable for long-term use of this drug, especially
highly flexible niosomes, known as elastic vesicles, have when used to treat rheumatic symptoms. The efficacy of
been proposed and are reported to be effective at delivering topical NSAIDs depends greatly on their capacity to penetrate
molecules through the skin, since edge activators (ie, ethanol) through the skin.
provide vesicles with elastic characteristics, which allow Nasr et al12 reported better stability and efficacy of their
them to penetrate more easily into the deeper layers of newly developed niosomes when compared liposomes for
the skin.33 Moreover, the major limitation of niosomes is targeting of aceclofenac via the skin. The anti-inflammatory
the liquid nature of the preparation, because when applied effect of aceclofenac vesicles was assessed using the rat
they may leak from the application site. This challenge can paw edema technique. The data showed that the entrap-
be overcome by incorporation of niosomes in an adequate ment efficiency and in vitro release of aceclofenac from

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Table 2 Summary of recent niosomal formulations developed for Nonionic surfactant vesicles have been prepared using
drug transdermal delivery Span 60 and cholesterol at different ratios for transdermal
TDDS Drug Reference delivery of meloxicam as an anti-inflammatory drug.39 Three
Niosomes Aceclofenac 12 different gel bases were also prepared (using poloxamer-407,
Diclofenac sodium 41
chitosan, and carbopol-934) and converted into niosomal gels.
Ketoprofen 43
Baclofen 47 The flux of meloxicam was found to be independent of the
Salidroside 48 viscosity of the formulations. The anti-inflammatory effects
Capsaicin 49 of meloxicam in the different niosomal gel formulations were
Resveratrol, alpha-tocopherol, 50
curcumin
evaluated using the carrageenan-induced rat paw edema
Alpha-tocopherol 57 method, which showed the superiority of niosomal gels over
Niosomal gel Aceclofenac 37 conventional gels.
Meloxicam 38, 39
Rofecoxib 42
Manosroi et al40 prepared novel elastic niosomes contain-
Simvastatin 53 ing entrapped diclofenac diethylammonium, an NSAID, for
Sulfadiazine sodium, propranolol 35 topical use. Various bilayer vesicular formulations composed
hydrochloride, tyrosol
Lopinavir 36 of dipalmitoylphosphatidylcholine, Tween 61, or Span 60
Elastic vesicles Sulfadiazine sodium 56 mixed with different molar ratios of cholesterol and ethanol
Elastic vesicle gel Diclofenac diethylammonium 40
at 0%–25% (v/v) were prepared. Elastic Tween 61 niosomes,
Papain 51
Proniosomes Vinpocetine 42 which had advanced physicochemical properties including no
Simvastatin 52 sedimentation, no layer separation, and unchanged particle
Nisoldipine 54
Nifedipine 55 size, were selected to entrap diclofenac diethylammonium.
Proniosomal gel Tenoxicam 44 The entrapment efficiency of the drug in the conventional and
Flurbiprofen 45 elastic Tween 61 niosomes was 65% and 93%, respectively.
Abbreviation: TDDS, transdermal drug delivery systems.
The deformability index values for the elastic niosomes were
markedly higher than for the conventional empty or loaded
the vesicles can be manipulated by varying the cholesterol niosomes, indicating the higher flexibility of the elastic
content, the type of surfactant used, and the type of charge. vesicles, especially when the drug was entrapped within the
Both vesicular systems had significant sustained anti- niosomes. Gel containing these elastic niosomes showed
inflammatory activity when compared with the marketed flux of diclofenac diethylammonium in the skin greater than
product, with niosomes being superior to liposomes, as that of the commercial Emulgel product, which contain an
manifested by edema and inhibition percentages, sug- equivalent amount of drug. The authors demonstrated the
gesting their effectiveness as topical anti-inflammatory enhancement of transdermal absorption through rat skin,
delivery systems. and also good anti-inflammatory activity in the rat ear edema
Aceclofenac niosomes have also been prepared using assay when diclofenac diethylammonium is entrapped in
Span 60 and cholesterol at different molar ratios for their novel elastic Tween 61 niosomes.
topical use after incorporation into carbopol gel.37 Data In 2014, Tavano et al41 investigated the effect of compart-
reported by Solanki et al37 showed that the gel improves mentalization of diclofenac sodium on the physicochemical
the penetration and therapeutic efficacy of the drug in all properties of niosomal vesicles when used as transdermal
niosomal gel preparations when compared with the plain carriers. Mixtures of Span 60/F127 and Tween 60/F127
gel formulation. Moreover, the niosome formulation could at different ratios were used to obtain the niosomes, with
act as a reservoir for a prolonged period and serve as a the objective of adding new experimental data regarding
penetration enhancer. the influence of the nature of the niosomal matrix on the
The study reported by El-Menshawe and Hussein38 physicochemical properties of niosomal vesicles and the
concerns transdermal delivery of meloxicam loaded into effect of compartmentalization of diclofenac sodium on drug
niosomes. Their data revealed that niosomes prepared from entrapment efficiency and skin permeability. The results
Span 60 and cholesterol had less side effects and there was demonstrated that all niosomes were spherical and homoge-
a marked increase in inhibition of edema in animals treated neous in shape. Their size was found to be dependent on the
with meloxicam vesicular gel when compared with animals hydrophile-lipophile balance of the surfactant mixture, ie, an
treated with free meloxicam. increase in hydrophobicity resulted in smaller vesicles. Drug

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Dovepress Niosomal drug delivery for transdermal targeting

incorporation led to a significant variation in vesicle size A novel sustained-release proniosomal system was
which was dependent on the whether the drug was located designed by El-Laithy et al using sugar esters as nonionic sur-
in the aqueous compartment or the bilayer compartment. In factants in which proniosomes were converted to niosomes
particular, niosomes that had the drug located into the aque- upon hydration of the skin following topical application
ous compartment showed the highest diameter, but when the under occlusive conditions.46 The vesicles were loaded with
drug was loaded into the bilayer, the vesicle size decreased vinpocetine, a potent anti-inflammatory agent that might also
slightly, and this trend was more pronounced when the drug have a potential role in the treatment of Parkinson’s disease
was located in both compartments at the same time. and Alzheimer’s disease. A number of in vitro parameters
Higher cumulative amounts of diclofenac permeated were studied, leading to an optimized formula that was
across rabbit skin after 24 hours were obtained by formula- assessed clinically for transdermal pharmacokinetics and skin
tions in which the drug was located in the aqueous core. The irritation. All formulations prepared showed high entrapment
data obtained indicate that changing the bilayer composi- efficiency and all vesicles were in a size range that favored
tion and drug compartmentalization offers the possibility efficient transdermal drug delivery. Taking into account
to modulate the physicochemical properties of the vesicles the high efficiency of systemic delivery together with the
and drug delivery. lack of irritation and excellent safety profile, laurate sugar
Rofecoxib is another NSAID that has been encapsulated ester proniosomes could be considered as very promising
in niosomes. In the work reported by Das and Palei,42 nio- candidates for enhancing the transdermal absorption and
somes were incorporated into a topical gel base for sustained penetration of vinpocetine.
therapeutic action. The vesicles were obtained using different Niosomes loaded with baclofen, a centrally acting muscle
sorbitan esters (Span 20, Span 40, and Span 60) and choles- relaxant, were prepared to improve the low skin penetration
terol. The results showed that these niosomes can be used as and poor bioavailability of conventional topical formulations
drug delivery carriers for targeting of rofecoxib to the skin. containing this drug.47 Vesicles were prepared by the lipid
The niosomal gel allowed prolonged drug release, thereby film hydration method using nonionic surfactant (Span 20)
sustaining the action of rofecoxib and reducing its adverse and cholesterol in different molar ratios. Vehiculation of
effects. Ketoprofen has also been encapsulated in niosomes baclofen by niosomal formulations resulted in improved
containing Span 60 for topical application, and was released muscle relaxant activity.
in a slow and sustained manner.43 Span 40-based niosomes were used as nanocarriers to
A new transdermal formulation of tenoxicam, charac- improve percutaneous absorption of salidroside, a phenyl-
terized by improved safety and high therapeutic efficacy, propanoid glycoside extracted from the root of Rhodiola
was developed by Ammar et al44 who designed a promising rosea, known for its pharmacological properties.48 Enhanced
proniosome gel formulation intended to reduce the daily dose permeation and skin deposition of salidroside were obtained,
of drug that needed to be administered, in an effort to improve due to the effects of the excipients used in the preparation
patient compliance. In this study, different proniosomal gel of the niosomes. Salidroside-loaded niosomes showed good
bases were prepared, characterized, and assessed for their biocompatibility with skin tissue, immortal human epidermal
drug entrapment efficiency, stability, effect on in vitro drug keratinocytes, and human embryonic skin fibroblasts, and in
release, and ex vivo drug permeation. This tenoxicam-loaded vitro cellular uptake experiments confirmed that these differ-
proniosomal formulation proved to be nonirritant, with signifi- ent types of skin cells had various channels for internalization
cantly higher anti-inflammatory and analgesic activity when of the nonionic surfactant vesicles.
compared with the oral tenoxicam tablets on the market. Capsaicin is readily absorbed from the skin upon topical
Flurbiprofen was formulated as a proniosomal transder- administration. Several capsaicin-based creams and patches
mal gel with high drug loading (55.4%, w/w) using a series are available as over-the-counter medications, usually
of nonionic surfactants (Span 20, Span 40, and Span 60) contain the drug at concentrations of 0.025%–1%, and are
and cholesterol.45 Data published by Zidan and Mokhtar45 commonly used for pain relief. Niosomal carriers have been
revealed that these proniosomes afforded high drug loading proposed for transdermal delivery of capsaicin. Vesicles
and skin permeation. In particular, maximum permeation were prepared using a defined ratio of Span 80 and Tween
values and minimum encapsulation efficiency were obtained 80 in order to obtain systems with a specific hydrophile-
by the formulation containing Span with a shorter fatty acid lipophile balance (10, 12, and 14) and were characterized
chain length and a minimum amount of cholesterol. in terms of dimension, morphology, and drug entrapment

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Muzzalupo and Tavano Dovepress

efficiency.49 Niosomes were compared with ­microemulsions proniosomes (composed of lecithin and Tween in a ratio of
prepared from the same surfactants to reach a similar 1:9) onto the skin significantly improved not only the bio-
hydrophile-lipophile balance. Data obtained by Tavano availability of the drug but also its hypocholesterolemic effect
et al49 revealed that better percutaneous capsaicin perme- in the treatment of hypercholesterolemic rats.
ation was achieved with niosomes when compared with The prevalence of childhood dyslipidemia is increasing
microemulsion-based formulations. This can be explained and is considered to be an important risk factor for cardio-
by the fact that the microemulsions were considerably more vascular disease in adulthood. To improve dosing accuracy
viscous than the niosomal suspensions, so that capsaicin and facilitate the determination of dosing regimens based
diffused faster from the niosomal matrix than from the on body weight, Zidan et al53 prepared a transdermal nio-
­microemulsions where the capsaicin molecule has to over- somal gel containing simvastatin as a possible transdermal
come the immiscible oil phase to reach the skin. drug delivery system for pediatric application. Transder-
Moreover, niosomes based on Tween 60 and containing mal administration of this niosomal gel in rats achieved a
resveratrol, alpha-tocopherol, and curcumin as single agents significant reduction in cholesterol and triglyceride levels
and in combination were designed with the aim of developing and an increase in plasma high-density lipoprotein concen-
novel cosmeceutical products.50 The results showed that coen- trations. These data show that this transdermal niosomal
capsulation of resveratrol/curcumin and alpha-tocopherol/ system not only has good potential for enhancing drug
curcumin affected the physicochemical properties of nio- bioavailability and hypolipidemic activity, but could also
somes and the entrapment efficiency values when compared be considered a promising antihyperlipidemic formulation
with the formulations containing the single antioxidant. The for pediatric use.
in vitro percutaneous permeation profiles for the antioxidants More recently, El Maghraby et al54 investigated the effect
appeared to be controlled and improved with respect to the of incorporation of skin penetration enhancers in proniosomes
corresponding free solutions used as controls. In addition, the on the ability of this system to deliver drugs transdermally. To
combination of antioxidants resulted in an improved ability achieve this objective, nisoldipine, a second-generation dihy-
to reduce free radicals due to a synergistic antioxidant action. dropyridine calcium antagonist, was selected as the model
Inhibition of free radicals was up to 40% for the resveratrol/ drug, based on the fact that nisoldipine suffers from low and
curcumin formulation, with the best performance being variable bioavailability after oral administration because of
achieved by the alpha-tocopherol/curcumin sample (about extensive first-pass metabolism in the liver. Lecithin, oleic
100% inhibition). However, the resveratrol/curcumin samples acid, and propylene glycol were used as enhancers to optimize
showed optimal performance in terms of cumulative amount transdermal delivery of nisoldipine from this provesicular
of antioxidants permeated across the skin. system and to design a new methodology to enhance its
Papain is a protease enzyme from Carica papaya latex, transdermal delivery. According to the published report, all
which is widely used in dermatology for the treatment of proniosomal formulations delivered the drug through the
scars. Manosroi et al51 compared the transdermal release skin at a significantly higher rate when compared with the
of papain from gel formulations containing niosomes or saturated aqueous control formulation and the enhancing
nanospheres. They demonstrated that niosomes (especially efficacy of the oleic acid/propylene glycol combination was
elastic niosomes obtained from Tween 61/cholesterol with even better than that of lecithin.
sodium cholate as an edge activator) could enhance transder- Nifedipine is a calcium channel blocker used extensively
mal absorption of papain through rat skin and improve scar in the treatment of angina and hypertension. After oral admin-
reduction in a rabbit ear model, which would be beneficial for istration, it undergoes extensive first-pass metabolism, which
development of topical products for the treatment of scars. limits both the amount of drug absorbed in the gastrointes-
Simvastatin is a lipid-lowering agent used in the treat- tinal tract and the bioavailability of the drug in the systemic
ment of hypercholesterolemia in humans and animals. When circulation. Yasam et al55 proposed the transdermal route as
administered orally, simvastatin undergoes extensive first-pass an alternative method of administration for nifedipine. In
metabolism in the liver, resulting in low bioavailability and this study, proniosomes were prepared by varying the ratios
a short half-life of only 2 hours. A proniosomal system for of Span 40, lecithin, aqueous phase, and polymer. Ex vivo
transdermal delivery of simvastatin was developed by Shaker percutaneous permeation studies in rat skin revealed the
et al52 and subjected to in vitro and in vivo characterization. role of niosomes as permeation enhancers. Moreover, skin
The results suggested that application of simvastatin-loaded irritation studies showed that when loaded into proniosomes,

30 submit your manuscript | www.dovepress.com Research and Reports in Transdermal Drug Delivery 2015:4
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Dovepress Niosomal drug delivery for transdermal targeting

nifedipine was not irritant and did not cause erythema, unlike Lopinavir, a highly potent protease inhibitor used in the
the pure drug. treatment of AIDS, needs to be coadministered with rito-
There has been a report of transdermal delivery of navir because of its high presystemic metabolism, which
niosomes loaded with sulfadiazine sodium, an antibiotic results in poor systemic bioavailability. In a study reported
usually used for the topical treatment of infected burns.56 by Patel et al,34 a niosomal gel was developed to improve the
In this study, the effects of inclusion of different amounts systemic availability of lopinavir via the transdermal route.
of ethanol, propylene glycol, and glycerol in the niosomes The niosomal formulation containing lopinavir, Span 40, and
were specifically evaluated. The presence of alcohol critically cholesterol contained a high amount of loaded drug with a
affected the physicochemical properties of niosomes, ie, minimum mean vesicular diameter. Encouraging results
vesicular size increased with amounts of alcohol, and at the in terms of niosomal stability, skin permeability, lack of
same alcohol concentration, bigger vesicles were obtained irritation, and ability to improve the overall bioavailability
with ethanol, followed by propylene glycol, and glycerol. of lopinavir led to the conclusion that niosomal gel has con-
Comparison of the percutaneous drug permeation profiles siderable promise as a novel transdermal nanocarrier for safe
showed that the cumulative amount of permeated sulfadiazine delivery of lopinavir into the systemic circulation.
sodium increased with alcohol concentration, up to 20% v/v; Despite the large amount of research published in recent
a higher concentration (40% v/v) resulted in a strong decrease decades, very few studies on topical niosomal formulations
in skin permeation. and their possible applications have progressed to patents and
Novel multicomponent formulations were studied by preclinical or clinical trials. Proniosomal gels loaded with
Tavano et al35 to evaluate the effect of the chemical struc- finasteride58 have undergone transdermal pharmacokinetic
ture of several surfactants and vehiculated drug on the evaluation, while urea59,60 and griseofulvin61 niosomal gels
physicochemical properties of the carriers and on percu- have reached the stage of clinical trials. Lancome and L’Oreal
taneous drug permeation profiles. Pluronic L64 or Aerosol have also developed a variety of antiaging products based on
OT were used as surfactants, and sulfadiazine sodium salt, niosomal formulations.
propranolol hydrochloride, and tyrosol were chosen as the
model drugs. Lyotropic liquid crystals were prepared at a Conclusion and future perspectives
fixed ratio between Pluronic L64 or Aerosol OT and water, This review offers a comprehensive explanation of the chemi-
in order to obtain lamellar lyotropic liquid crystal phases, cal composition, structure, advantages, and applications of
and the corresponding surfactant was used to prepare the niosomes, their role as percutaneous permeation enhancers,
vesicular systems (niosomes) that were added to the gel. All and their recent applications as delivery systems for trans-
the studied formulations, such as gel-niosome systems, nio- dermal drug targeting. Niosomes have been demonstrated to
somal suspensions and gels, act as percutaneous permeation be promising controlled delivery systems for percutaneous
enhancers respect to the corresponding free drug solutions administration of both hydrophilic and lipophilic drugs. The
used as control. potential of niosomes can be enhanced by using novel prepa-
Another interesting study was reported by Kong et al57 in ration, loading, and modification methods. These areas need
which functionalized niosomes were used as a transdermal further exploration and research for the development of nio-
drug delivery system for tumor therapy. These investigators somal preparations that can be made commercially available.
have developed a novel drug nanocarrier based on hyaluronic Researchers should be alert in the need for appropriate
acid and niosomes, which promotes transdermal drug selection of suitable surfactants for preparation of niosomes,
delivery and has tumor-targeting ability. An amphiphilic given that the type of surfactant used is the main parameter
hyaluronic acid esterified with glycerol monostearate was determining the successful formation of these vesicles, along
prepared and self-assembled onto the niosome surface to with their toxicity, stability, and potential applications.
give hyaluronic acid niosomes. Their results showed that
incorporation of hyaluronic acid significantly promoted endo- Disclosure
cytosis of the nanocarriers into tumor cells. Hyaluronic acid The authors report no conflicts of interest in this work.
niosomes may be considered not only as efficient and safe
carriers for transdermal permeation, but may also represent References
1. Uchegbu IF, Florence AT. Nonionic surfactant vesicles (niosomes):
a useful and promising device for tumor therapy through physical and pharmaceutical chemistry. Adv Colloid Interface Sci.
percutaneous administration. 1995;58:1–55.

Research and Reports in Transdermal Drug Delivery 2015:4 submit your manuscript | www.dovepress.com
31
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Muzzalupo and Tavano Dovepress

2. Moghassemi S, Hadjizadeh A. Nano-niosomes as nanoscale drug 25. Karande P, Mitragotri S, Enhancement of transdermal drug delivery
delivery systems: an illustrated review. J Control Release. 2014;185: via synergistic action of chemicals. Biochim Biophys Acta. 2009; 1788:
22–36. 2362–2373.
3. Lasic DD. On the thermodynamic stability of liposomes. J Colloid 26. Bouwstra JA, Honeywell-Nguyen PL. Skin structure and mode of action
Interface Sci. 1990;140:302–304. of vesicles. Adv Drug Deliv Rev. 2002;54:41–55.
4. Gannu PK, Rajeshwarrao P. Nonionic surfactant vesicular systems 27. Muzzalupo R, Tavano L, Cassano R, Trombino S, Ferrarelli T, Picci N.
for effective drug delivery an overview. Acta Pharmacol Sin. 2011; 1: A new approach for the evaluation of niosomes as effective transdermal
208–219. drug delivery systems. Eur J Pharm Biopharm. 2011;79:28–35.
5. Mahale NB, Thakkar PD, Mali RG, Walunj DR, Chaudhari SR. 28. Manconi M, Sinico C, Valenti D, Lai F, Fadda AM. Niosomes as car-
Niosomes: novel sustained release nonionic stable vesicular systems – riers for tretinoin. III. A study into the in vitro cutaneous delivery of
an overview. Adv Colloid Interface Sci. 2012;183:46–54. vesicle-incorporated tretinoin. Int J Pharm. 2006;27:11–19.
6. Obata Y, Takayama K, Maitani Y, Machida Y, Nagai T. Effect of ethanol 29. Abdelkader H, Alani AW, Alany RG. Recent advances in non-ionic
on skin permeation of nonionized and ionized diclofenac. Int J Pharm. surfactant vesicles (niosomes): self-assembly fabrication, characteriza-
1993;89:191–198. tion, drug delivery applications and limitations. Drug Deliv. 2014;21:
7. Perche F, Torchilin VP. Recent trends in multifunctional liposomal 87–100.
nanocarriers for enhanced tumor targeting. J Drug Deliv. 2013; 2013: 30. Mali N, Darandale S, Vavia P. Niosomes as a vesicular carrier for topi-
705265. cal administration of minoxidil: formulation and in vitro assessment.
8. Pawar SD, Pawar RG, Kodag PP, Waghmare AS. Niosome: an unique Drug Deliv Transl Res. 2013;3:587–592.
drug delivery system. International Journal of Biology, Pharmacy and 31. Cevc G. Lipid vesicles and other colloids as drug carriers on the skin.
Allied Sciences. 2012;3:406–416. Adv Drug Deliv Rev. 2004;56:675–711.
9. Khan A, Sharma PK, Visht S, Malviya R. Niosomes as colloidal drug 32. El Maghraby GM, Barry BW, Williams AC. Liposomes and skin:
delivery system: a review. Journal of Chronotherapy and Drug Delivery. from drug delivery to model membranes. Eur J Pharm Sci. 2008;34:
2011;2:15–21. 203–222.
10. Florence AT, Baillie AJ. Nonionic surfactant vesicles – alternatives to 33. Touitou E, Dayan N, Bergelson L, Godin B, Eliaz MJ. Ethosomes –
liposomes. In: Prescott LF, Nimmo WS, editors. Novel Drug Delivery novel vesicular carriers for enhanced delivery: characterization and
and its Therapeutic Application. New York, NY, USA: John Wiley and skin penetration properties. Control Release. 2000;65:403–418.
Sons Ltd; 1989. 34. Patel KK, Kumar P, Thakkar HP. Formulation of niosomal gel for
11. Thakur V, Arora S, Prashar B, Vishal P. Niosomes and liposomes – enhanced transdermal lopinavir delivery and its comparative evaluation
vesicular approach towards transdermal drug delivery. Interna- with ethosomal gel. AAPS Pharm Sci Tech. 2012;13:1502–1510.
tional Journal of Pharmaceutical and Chemical Sciences. 2012;1: 35. Tavano L, Gentile L, Oliviero Rossi C, Muzzalupo R. Novel gel-niosome
981–993. formulations as multicomponent systems for transdermal drug delivery.
12. Nasr M, Mansour S, Mortada ND, Elshamy AA. Vesicular aceclofenac Colloids Surf B Biointerfaces. 2013;110:281–288.
systems: a comparative study between liposomes and niosomes. 36. Alsarra IA, Bosela AA, Ahmed SM, Mahrous GM. Proniosomes as
J Microencapsul. 2008;25:499–512. a drug carrier for transdermal delivery of ketorolac. Eur J Pharm
13. Handjani-Vila RM, Riber A, Rondot B, Valenberghe G. Aqueous Biopharm. 2005;59:485–490.
dispersion. Int J Cosmet Sci. 1979;1:303–314. 37. Solanki AB, Parikh JR, Parikh RH, Patel MR. Evaluation of different
14. Barel A, Paye M, Maibach HI. Handbook of Cosmetic Science and compositions of niosomes to optimize aceclofenac transdermal delivery.
Technology. New York, NY, USA: Marcel Dekker Inc.; 2001. Asian Journal of Pharmaceutical Sciences. 2010;5:87–95.
15. Singh S. Niosomes: a role in targeted drug delivery system. Int J Pharm 38. El-Menshawe SF, Hussein AK. Formulation and evaluation of meloxi-
Sci Res. 2013;4:550–557. cam niosomes as vesicular carriers for enhanced skin delivery. Pharm
16. Vyas SP, Khar RK. Novel carrier systems. In: Jain NK, editor. Targeted Dev Technol. 2013;18:779–786.
and Controlled Drug Delivery. New Delhi, India: CBS Publishers and 39. El-Badry M, Fetih G, Fathalla D, Shakeel F. Transdermal delivery of
Distributors Pvt Ltd; 2010. meloxicam using niosomal hydrogels: in vitro and pharmacodynamic
17. Sahin NO. Niosomes as nanocarrier systems. In: Mozafari MR, evaluation. Pharm Dev Technol. 2014;9:1–7.
editor. Nanomaterials and Nanosystems for Biomedical Applications. 40. Manosroi A, Jantrawuta P, Manosroi J. Anti-inflammatory activity
New York, NY, USA: Springer; 2007. of gel containing novel elastic niosomes entrapped with diclofenac
18. Hofland HE, Bouwstra JA, Verhoef JC, et al. Safety aspects of non-ionic diethylammonium. Int J Pharm. 2008;360:156–163.
surfactant vesicles: a toxicity study related to the physicochemical 41. Tavano L, de Cindio B, Picci N, Ioele G, Muzzalupo R. Drug compart-
characteristics of non-ionic surfactants. J Pharm Pharmacol. 1992; mentalization as strategy to improve the physico-chemical properties
44: 287–294. of diclofenac sodium loaded niosomes for topical applications. Biomed
19. Pape WJ, Pfannenbecker U, Hoppe U. Validation of the red blood cell Microdevices. 2014;16:851–858.
test system as in vitro assay for the rapid screening of irritation potential 42. Das MK, Palei NN. Sorbitan ester niosomes for topical delivery of
of surfactants. Mol Toxicol. 1987;1:525–536. rofecoxib. Indian J Exp Biol. 2011;49:438–445.
20. Tavano L, Infante MR, Abo Riya M, et al. Role of aggregate size in 43. Rajnish A, Ajay S. Release studies of ketoprofen niosome. J Chem
the hemolytic and antimicrobial activity of colloidal solutions based Pharm Res. 2010;1:79–82.
on single and gemini surfactants from arginine. Soft Matter. 2013;9: 44. Ammar HO, Ghora M, El-Nahhas SA, Higazy IM. Proniosomes as
306–319. a carrier system for transdermal delivery of tenoxicam. Int J Pharm.
21. Paolino D, Muzzalupo R, Ricciardi A, Celia C, Picci N, Fresta M. In 2011;405:142–152.
vitro and in vivo evaluation of bola-surfactant containing niosomes for 45. Zidan AS, Mokhtar M. Multivariate optimization of formulation
transdermal delivery. Biomed Microdevices. 2007;9:421–433. variables influencing flurbiprofen proniosomes characteristics. J Pharm
22. Walker RB, Smith EW. The role of percutaneous penetration enhancers. Sci. 2011;100:2212–2221.
Adv Drug Deliv Rev. 1996;18:295–301. 46. El-Laithy HM, Shoukry O, Mahran LG. Novel sugar esters proniosomes
23. Barry BW. Lipid protein partitioning theory of skin penetration for transdermal delivery of vinpocetine: preclinical and clinical studies.
enhancement. J Control Release. 1991;15:237–248. Eur J Pharm Biopharm. 2011;77:43–55.
24. Schreier H, Bouwstra J. Liposomes and niosomes as topical drug car- 47. Keservani RK, Sharma AK, Ramteke S. Novel vesicular approach for
riers: dermal and transdermal drug delivery. J Control Release. 1994; topical delivery of baclofen via niosomes. Lat Am J Pharm. 2010; 29:
30:1–15. 1364–1370.

32 submit your manuscript | www.dovepress.com Research and Reports in Transdermal Drug Delivery 2015:4
Dovepress
Dovepress Niosomal drug delivery for transdermal targeting

48. Zhang Y, Zhang K, Wu Z, et al. Evaluation of transdermal salidroside 55. Yasam VR, Jakki SL, Natarajan J, et al. Novel vesicular transdermal
delivery using niosomes via in vitro cellular uptake. Int J Pharm. 2015; delivery of nifedipine – preparation, characterization and in vitro/in-
478:138–146. vivo evaluation. Drug Deliv. 2014;9:1–12.
49. Tavano L, Alfano P, Muzzalupo R, de Cindio B. Niosomes vs 56. Muzzalupo R, Tavano L, Lai F, Picci N. Niosomes containing hydroxyl
microemulsions: new carriers for topical delivery of capsaicin. Colloids additives as percutaneous penetration enhancers: effect on the transder-
Surf B Biointerfaces. 2011;87:333–339. mal delivery of sulfadiazine sodium salt. Colloids Surf B Biointerfaces.
50. Tavano L, Muzzalupo R, Picci N, de Cindio B. Co-encapsulation of 2014;123:207–212.
lipophilic antioxidants into niosomal carriers: Percutaneous permeation 57. Kong M, Park H, Feng C, Hou L, Cheng X, Chen X. Construction of
studies for cosmeceutical applications. Colloids Surf B Biointerfaces. hyaluronic acid niosome as functional transdermal nanocarrier for tumor
2014;114:114–149. therapy. Carbohydr Polym. 2013;94:634–641.
51. Manosroi A, Chankhampan C, Manosroi W, Manosroi J. Transdermal 58. Kassem MA, Esmat S, Bendas ER, El-Komy MH. Efficacy of
absorption enhancement of papain loaded in elastic niosomes incor- topical griseofulvin in treatment of tinea corporis. Mycoses. 2006;49:
porated in gel for scar treatment. Eur J Pharm Sci. 2013;48:474–483. 232–235.
52. Shaker DS, Nasr M, Mostafa M. Bioavailability and hypocholester- 59. Lakshmi PK, Bhaskaran S. Phase II study of topical niosomal urea
olemic effect of proniosomal simvastatin for transdermal delivery. gel – an adjuvant in the treatment of psoriasis. International Journal
International Journal of Pharmacy and Pharmaceutical Sciences. 2013; of Pharmaceutical Sciences Review and Research. 2011;7:1–7.
5:344–351. 60. Mazda F, Özer AY, Ercan MT. Preparation and characterisation of
53. Zidan AS, Hosny KM, Ahmed OA, Fahmy UA. Assessment of sim- urea niosomes – in vitro and in vivo studies. STP Pharm Sci. 1997;7:
vastatin niosomes for pediatric transdermal drug delivery. Drug Deliv. 205–214.
2014;11:1–14. 61. Ribeiro de Souza AL, Kiill CP, Kolenyak dos Santos FK, et al.
54. El Maghraby GM, Ahmed AA, Osman MA. Penetration enhancers in Nanotechnology-based drug delivery systems for dermatomycosis
proniosomes as a new strategy for enhanced transdermal drug delivery. treatment. Curr Nanosci. 2012;8:512–519.
Saudi Pharm J. 2015;23:67–74.

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