Chapter6 CosmeceuticalsandNaturalCosmetics

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Cosmeceuticals and Natural Cosmetics
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126 Recent Trends in Research into Malaysian Medicinal Plants
6
Cosmeceuticals and Natural
Cosmetics
Azila Abd. Aziz, Zarani Mat Taher, Rohaiza Muda and
Ramlan Aziz
6.1 INTRODUCTION
It is human nature to desire beauty. As such, the use of cosmetics

and personal care products can be traced back to ancient times
where ingredients such as milk, honey, lemon juice, clay, mud and
even arsenic have been used in the name of beauty. In the present
days, the cosmetics and personal care industry is a vital industry
that contributes significantly to the world gross domestic product
(GDP). Figure 1 shows the snapshot of the global market size for
the cosmetics, toiletry and fragrance industry for 2010 [1].
Figure 1 Classification of the cosmetic and personal care industry and its
global market size in 2010 [1]
Cosmeceuticals and Natural Cosmetics 127
There are three major trading blocks for cosmetics namely

the USA, Europe and Japan. The Food, Drug and Cosmetic Act [2]
defines cosmetics as ‘articles intended to be rubbed, poured,
sprinkled, or sprayed on, introduced into, or otherwise applied to
human body for cleansing, beautifying, promoting attractiveness,
or altering the appearance without affecting structure or function’.
European Directive 93/35/EEC [3] defines cosmetic products as
‘any substance or preparation intended to be placed in contact with
the various external parts of the human body (epidermis, hair
system, nails, lips and external genital organs) or with teeth and the
mucous membranes of the oral cavity with a view exclusively or
mainly to cleaning them, perfuming them, changing their
appearance and/or correcting body odours and/or protecting them
or keeping them in good conditions’. Japanese pharmaceutical
affairs law defines cosmetics as ‘any article intended to be used by
means of rubbing, sprinkling or by similar application to the
human body for cleansing, beautifying, promoting attractiveness
and altering appearance of the human body, and for keeping the
skin and hair healthy, provided that the action of the article on the
human body is mild’ [4]. These definitions are quite similar in that
all of them classify cosmetics as products that enhance appearance
but do not have any therapeutic benefits as opposed to drugs. Thus,
a new term, cosmeceuticals, has been coined. Cosmeceuticals
represent a hybrid between cosmetics and drugs and they stand for
products that contain active ingredients capable of altering
structure or function [5, 6]. Some cosmeceutical products are
covered under the category of quasidrug in Japan [4].
Cosmeceuticals can be naturally derived or chemically
synthesized. Ideally, cosmeceuticals ingredients must be safe,
efficacious, novel, stable, inexpensive to manufacture and can be
metabolized within skin [7]. Information on cosmeceuticals active
ingredients is abundant in literature. In this chapter, the substances
are reviewed based on their classifications as ingredients for skin
care, sun care or hair care.
6.2 SKIN COSMECEUTICALS
Skin is a physical barrier that protects the internal environment

from the external one. Structurally, skin has two main layers: the
epidermis and the dermis. The epidermis serves as the physical and
chemical barrier and the dermis provides structural support.
The epidermis is the thin outer layer, which has either four
or five layers of cells depending on exposure to friction [8]. The
five layers from superficial to the deepest are stratum corneum,
stratum lucidum, stratum granulosum, stratum spinosum and
stratum basale. The stratum corneum consists of 25-30 stacked
sheets of flat, dead cells completely filled with keratin. It is
continually renewed via the desquamation process. Keratinocytes,
which are about 90% of the epidermal cells, from the basal layers
migrate to the surface, turn into cornified, anucleated cells and are
sloughed off. The process takes about four weeks.
The dermis is composed of collagen and elastic fibers [8].
The outer portion of the dermis is the papillary region, which
consists of connective tissues containing fine elastic fibers. The
inner portion is the reticular layer consisting of dense, irregular
connective tissues containing collagen and coarse elastic fibers.
The reticular layer provides skin with strength, extensibility and
elasticity.
Protecting and preserving the skin is important.
Environmental elements, ultraviolet radiation, air pollutions and
natural aging process can alter the barrier properties of the skin.
The stratum corneum cells of a healthy skin are cemented by a
mixture of ceramides, cholesterol, free fatty acids, triglycerides,
cholesterol sulfate and water [9, 10]. This constitutes the lipid
barrier of the skin. Damage in the stratum corneum barrier function
will result in dry, flaky and rough skin that is easily irritated [11].
Damage to the living epidermis will affect the barrier function
ability of the skin [12]. The dermis corresponds to 85-90% of skin
tissue. Damage to this layer, which provides structural support to
skin, will result in wrinkles, stretch marks or thin and flaccid skin
[12].
For optimal skin care, Lintner et al. [12] have suggested the
following methods: strengthen the cement of the stratum corneum,
stimulate the synthesis and renewal of the stratum corneum layer
and renew the dermal tissue. Various skin cosmeceuticals have
been used to address these issues. Apart from that, some skin
cosmeceuticals have also been used to block the production of
melanin and thus tone down brown marks, liver spots, melasma
etc.
6.2.1 Moisturizers
Moisturizers that increase hydration and make stratum corneum

softer and supple can also be considered cosmeceuticals.
Moisturizers can improve skin barrier function by affecting stratum
corneum architecture and skin barrier homeostasis through
reduction of transepidermal water loss (TEWL), increased skin
hydration and decreased proliferative activity of epidermis [13].
Creams are usually the delivery method of choice for moisturizers.
Moisturizers contain fats, oils, humectants, emulsifiers and
preservatives. Common fats and oil for moisturizers are mineral
oils, waxes, long-chain esters, fatty acids, lanolin, and mono-, di-
and triglycerides. Humectants are substances with water attracting
properties. One important group of humectants is the α-hydroxy
acids [14]. Other substances used are urea, glycerin, propylene
glycol and pyrrolidone carboxylic acid [13].
6.2.2 Retinoids
Retinoids are one of the most common and popular cosmeceuticals

ingredients in the market. Retinoids are vitamin A and its natural
and synthetic derivatives. Naturally occurring retinoids are retinol,
retinal and retinoic acid. Retinoids analogues that have been
synthesized are tretinoin (also occurs naturally), isotretinoin,
etretinate, etetrin, arotinoid, arotinoid ethyelster, arotinoid methyl
sulfone and adapalene. Retinoids have adverse effects associated

with hypervitaminosis A [15]. The most significant effect is
teratogenicity. Topical delivery systems, however, offer a safer
adverse effect profile [16].
Retinoids have been used in the treatment of clinical
conditions such as psoriasis, acne vulgaris, leukemia and squamous
cell carcinoma; however, for cosmeceuticals, natural retinoids are
the preferred choices [16]. Retinoids function as antioxidants and
they can also activate specific genes and proteins, and as such the
main role of retinoids in cosmeceuticals is for photoaging [17, 18].
FDA has approved retinoic acid for the treatment of acne, fine skin
wrinkle and reduction of liver spots [19-21]. However, retinol is a
more popular ingredient in cosmetic preparations, as it has been
shown to be less irritating topically compared to retinoic acid and it
is also a nonprescription preparation [22]. Retinol and its esters
have been shown to penetrate the skin [23], to be taken up by the
cells [24], and to be metabolized in the epidermis and dermis [25].
6.2.3 Hydroxy Acids
Hydroxy acids are also very popular as cosmeceuticals ingredients.

They are widely found in on-the-shelf cosmetic formulations.
Hydroxy acids are organic carboxylic acids. According to their
molecular structure, they are classified as α-hydroxy acids (AHA)
and β-hydroxy acids (BHA). AHAs can be simple aliphatic
compounds or complex molecules. They are usually referred to as
fruit acids. Examples of AHAs are glycolic acid, lactic acid,
mandelic acid, malic acid, tartaric acid and citric acid. BHAs are
aromatic compounds. The different BHAs include salicylic acid,
tropic acid and LHA (2-hydroxy-5-octanoyl benzoic acid).
Despite their popularity, many aspects of the mechanisms
of action of hydroxy acids remain unknown and are contradictory
in some facets. One part of its biological activities may be
attributed to the inherent acid strength of the compound. However,
it does not correlate with the overall potency of the final
formulation [26].
Clinically, both AHAs and BHAs exert direct effects on
stratum corneum affected by xerosis and ichthyosis [27]. AHAs
can cause necrosis when applied to the skin at high concentrations
resulting in a chemical peel [28]. Glycolic acid peel is used in the
adjunctive treatment of epidermal hypermelanosis [29]. Salicylic
acid can be used to treat acne [30]. Hydroxyacids have also been
reported to boost the physiology of the epidermis and dermis [31-
32] resulting in the correction of skin atrophy [33], the reduction of
pigmentary changes [34] and the reduction of wrinkles of fine and
moderate depth [35, 36].
Even though AHAs and BHAs are widely used in
dermatology and cosmetology as preventive measures and
adjunctive therapy, much remains to be learned. Consumers should
also be careful and should strictly follow instructions as adverse
reactions particularly in relation to greater sensitivity to ultraviolet
radiation exposure has been reported [37].
6.2.4 Botanicals
The current trend in cosmetics embraces the back to nature

concept. Accordingly, botanical extracts are another popular
ingredient in cosmeceuticals. Most of the time, active ingredients
are not present in equal amounts in all parts of a plant and thus,
usually only one part of the plant is used. Compared to the drug
industry, in the cosmetic industry, total extracts are usually
employed as active ingredients.
Botanicals have been used as antioxidants in
cosmeceuticals. Vegetable oils such as wheat germ oil and palm oil
are rich in tocopherols and tocotrienols. A unicellular microalgae,
Dunaliella, can be a source of caretenoids. Their β-carotene
concentrations can increase by ten times to about 14% of their dry
weight under extreme conditions [38]. Rosa canina (dog rose)
fruits, kiwi fruits and Malphigia punicifolia (West Indian cherry)
are rich in ascorbic acid, which have been reported to improve cell
resistance, to degrade histamine, to protect against free-radical

damage, to help maintain skin elasticity and to have immuno-
stimulating activity [38]. Gingko, Fagopyrum (buckwheat),
Eucalyptus sambucus (European elder) and Sophora japonica are
rich in flavonoids [39]. Gingko biloba extract has been found to
locally induce superoxide dismutase (SOD) and catalase after
topical application [40]. Rosemary extracts are rich in carnosic
acid, which has been used to protect food [38]. Extracts of
Syzygium aromaticum and Germanium thumbergii have been used
to protect the skin extracellular matrices from free radicals [41].
Botanicals are also used to help maintain the skin lipid
barrier. Evening primrose, borage and black currant are rich in
polyunsaturated fatty acids of the n-6 type [38]. They are important
in bringing essential fatty acids to the skin. Oil and plant butters
are rich in essential fatty acids, which can protect skin and reduce
water loss. Plant phytosterols can be used for optimized barrier
repair in skin. A sterol enriched fraction from canola oil showed
beneficial effects on the skin barrier in murine skin [42]. Yeast,
wheat, potato, rice bran and white mulberry are rich in ceramides
and glycoceramides [38].
Botanicals have also been used in cosmeceuticals for anti-
aging. Extracts of black currants, Centella asiatica and Areca have
free-radical scavenging properties that can protect collagen and
elastin [38]. Chamomile contains apigenin, which have anti-
inflammatory properties that can protect mucopolysaccharides
from degradation [38]. Curcumin has anti-inflammatory activity by
inhibiting leukotriene formation, inhibiting platelet aggregation
and stabilizing neutrophilic lysosomal membranes [40].
Glycyrrhizin from licorice roots is used for its anti-inflammatory
properties. It inhibits the pro-inflammatory activities of
prostaglandins and leukotrienes [40]. Amino acids from plant
extracts can be used for stimulation of systems that are active in
aging and it is important in the protection of the skin barrier
function [43, 44]. Melanocyte stimulating hormone (MSH), which
decreases rapidly with age, can be found in oats, corn, rice and
ginger [45]. Hydroxyacids used for epidermal shedding, hydration

and cell renewal are usually obtained from fruits. Oligoelements
and minerals in horsetail and rice are important in the synthesis of
collagen and proteoglycans [46]. Ganoderma extracts have
immuno-stimulating and immuno-regulating properties and have
been used in traditional Chinese medicine to slow down aging
[38].
6.2.5 Amino Acids and Derivatives
Amino acids are molecules with an amino group and a carboxylic

group. They are the building block of protein and they are supplied
to the living cells via blood circulation. With regard to the skin,
amino acids are supplied to the fibroblast cells in the dermis. Then,
through intercellular liquid channel, they are supplied to
keratinocyte, melanocyte and other cells in the epidermis [47].
Amino acids are also a constituent of materials called natural
moisturizing factor (NMF) that are responsible for skin hydration
control. NMF are the end metabolites of the enzymatic digestion of
filaggrin, a protein responsible for aggregating keratin and other
proteins in the upper layer of the epidermis to form the stratum
corneum [48]. Alanine and serine were found to stimulate
activation of enzymes for desquamation [49].
Amino acids play important physiological roles for the
generation and integration of skin function. Application of
ointment with an amino acid mixture to skin after surgery had
resulted in improved healing with decreased keloid formation [50].
Proline has been combined with lactate and pyrroridone carboxylic
acid to formulate NMF moisturizers [51]. Amino acid derivatives
can also be utilized for skin care products. Cholesterol esters of N-
acylamino acid have been developed as novel emollients with
functions that are similar to ceramides [52]. Conjugates of amino
acids with naphtylaldehyde or salicyldehyde have been used as
antioxidants with iron sequestering capacity to reduce UV-induced
oxidative stress [53]. A conjugate of N-(4-pyridoxylmethylene)-L-
serine and vitamin B6 has also been developed for a functional

cosmetic antioxidant [54].
6.2.6 Depigmentation Agents
Facial pigmentary disorders can be acquired (melasma, sun

tanning, solar lentigo etc.), hereditary (nevus pigmentosus, nevus
spilus, nevus of ota or ephelid) or a result of skin tumors
(melanoma, basal cell carcinoma etc.) [55]. Hyperpigmentation can
be due to melanocytosis (increased number of melanocytes) or
melanosis (increased number of melanin). Melasma, non-
inflammatory hyperpigmentation around eyes, mouth, cheeks and
forehead that does not result in itching or irritation, is usually
suffered by middle aged women with an average age of 43.
Melasma is mainly a result of increased progesterone level in
serum at luteal phases [56]. Histopathology of melasma shows
increased melanin pigment especially in the supranuclear region of
the basal cells. However, epidermal melanocytes have not
increased and thus the hyperpigmentation of melasma is deemed
reversible [55].
Depigmenting agents can be divided into phenolic
compounds, non-phenolic compounds or combination formulas
[57-65]. Phenolic compounds include hydroquinone,
monobenzylether of hydroquinone, 4-methoxyphenol, 4-
isopropylcatechol, N-2,4-acetoxylphenyl thioethyl acetamide and
N-acetyl-4-w-cyteaminylphenol. Non-phenolic compounds include
corticosteroids, tretinoin, azelaic acid, N-acetylcystein, L-ascorbyl-
2-phosphate and kojic acid. Combination formulas include
Kligman’s formula, Pathak’s formula and Westerhof’s formula.
Hydroquinone is an ingredient derived from plants and has
been used in cosmetics as a skin lightener. The skin lightening
properties of hydroquinone is due to the inhibition of melanocyte
tyrosinase [57]. However, hydroquinone has been associated with
cancer scare and exogenoeus ochronosis, a condition that results in
the skin becoming dark and thick, resulting in the ban of the
ingredient in Japan, EU and Australia in 2001 and a proposed ban

by FDA in 2006.
Corticosteroid or topical steroids are sometimes used as
depigmentation agents. Their effects on pigmentation are mediated
via the initial local vasoconstriction when it applied to the skin.
Their use however need to be highly regulated as they can be
responsible for producing severe side effects associated with skin
bleaching. This give the impression of immediate reduction in
pigmentation of the skin [66]. Eventually, they prevent epidermic
melanogenesis. The many adverse effects when prolonged used on
thin skin (facial and flexural site) include peri-oral dermatitis,
development of striate, acne vulgaris etc [67-69].
Kojic acid is a fungal metabolic product that has been used
as a skin-depigmenting agent in cosmetics. Kojic acid acts by
inhibiting tyrosinase activity through its ability to chelate the
copper required by tyrosinase [70].
Azelaic acid is a dicarboxylic acid derived from
Plasmodium ovale, a mushroom [62]. Azelaic acid can selectively
inhibit tyrosinase activity in hyperactive melanocytes. It does not
have any significant activity on normal skin. However, it is less
effective than hydroquinone and is usually used in combination
with tretinoin or topical steroids [71].
6.3 SKIN COSMECEUTICALS: SUN CARE
The ozone layer protects the living organisms on earth from the
harmful ultraviolet (UV) rays. The depletion of the ozone layers,
mainly due to the release of the man-made group of compounds
called chlorofluorocarbons (CFCs), has resulted in increased
exposure to UV radiation. The skin, being the outermost organ of
the body, suffers the most. Skin responses to UV radiation are
classified as acute and chronic. Acute reaction resulted in sunburn
and sun tan [72]. Prolonged exposure to the sun causes damage in
collagen, elastin and function of fibroblast resulting in photoaging.
The pathology of photoaged skin has been associated with a

chronic wound in which remodeling is incomplete due to the huge
amount of surface area involved and the complication of ongoing
sun exposure [73].
UV rays are electromagnetic waves with wavelengths of
100–400 nm. They are classified as vacuum UV (100–190 nm),
UVC (190–290 nm), UVB (290–320 nm) and UVA (320–400 nm).
Only UVB and UVA reach the earth. UVB is absorbed in the
epidermis, and UVA penetrates deep into the skin [74]. Reactive
oxygen species (ROS) are generated by UV irradiation. The ROS
generated by UV irradiation include singlet oxygen, (1O2),
superoxide anion (O2-), hydrogen peroxide (H2O2), hydroxyl
radical (.OH) and nitric oxide (NO). ROS and other free radicals
are also continuously produced during physiological cellular
metabolism.
6.3.1 Antioxidant Defense Systems
To counteract the harmful effects of ROS the skin is equipped with

antioxidant systems. Humans can synthesize some antioxidants
such as glutathione or ubiquinol-10 but some antioxidants such as
vitamin C and vitamin E have to be supplied by dietary intake.
Antioxidants work by scavenging free radicals, scavenging lipid
peroxyl radicals, binding metal ions and by removing oxidatively
damaged biomolecules [75]. However, the antioxidant defense in
cutaneous tissue can be overwhelmed by an increased onslaught of
exposure to oxidative stress whether exogenously or endogenously
resulting in damage to biomolecules such as lipids, proteins and
nucleic acids.
L-ascorbic acid is also known as vitamin C. Some
mammals can synthesize vitamin C but humans require dietary
intake of this vitamin. Vitamin C is a water-soluble antioxidant
that acts as a reductant in the hydroxylation of procollagen, proline
and lysine [76]. Vitamin C has been used to stimulate collagen
repair, thus minimizing the effects of photoaging. However,
transport of topically applied vitamin C needs sophisticated

vehicles such as triple emulsions as vitamin C is unstable and can
easily degrade [77].
Another water-soluble antioxidant is glutathione. It is a
tripeptide of glutamic acid, cysteine and glycine and is produced by
cells. GSH (γ-glutamyl- cysteinyl-glycine) protects cells by
reacting directly with ROS resulting in the subsequent formation of
glutathione disulfide (GSSG). The ratio of GSH/GSSG is normally
greater than 100 [78]. The GSH/GSSG ratio can decrease due to
oxidative stress. A high GSH/GSSG ratio could be essential for the
stratified and keratinized epidermis however topically applied GSH
penetrates skin poorly and does not effectively prevent
photodamage [79].
Uric acid is a small water-soluble antioxidant, which is the
end product of purine metabolism. It is a powerful scavenger of
singlet oxygen, peroxyl radical, hydroxyl radical ozone and
hypochlorous acid [80-82]. Urate can also stabilize the effect of
reduced concentration of vitamin C in serum.
Vitamin E is the major lipid-soluble antioxidant in plasma,
membranes and tissue [83]. Vitamin E refers to eight types of
molecules, four tocopherols and four tocotrienols, which exhibit
vitamin E activity. Its major role is generally considered to be the
arrest of chain propagation in lipid peroxidation by scavenging
lipid peroxyl radicals [84]. This protects the cell membrane from
destruction. When vitamin E is applied before UV irradiation,
acute skin responses such as erythema, edema and sunburn cell
formation were reduced [85-86]. Topical application of vitamin E
also reduced chronic skin reaction such as skin wrinkling [87].
Vitamin E may also have substantial sunscreening properties [88].
Topically applied vitamin E had been shown to penetrate into
dermal layers and protect the dermal components in human skin
and thus prevent photoaging [89-90]. Topical formulations
containing α-tocopherol from 0.1% to 1.0% are likely to be
effective in enhancing antioxidant protection of the skin barrier as
less than 0.2% α-tocopherol in rinse-off products were shown to
increase levels of vitamin E in stratum corneum of human skin and

protected against lipid peroxidation in vivo [91].
Superoxide dismustase (SOD) is an enzymatic antioxidant.
Topical administrations of SOD resulted in reduction of PUVA-
induced skin reactions in guinea pig [92], murine [93] and human
skins [94].
Lipoic acid is a unique free radical protector, which is fat
and water soluble. It can be broken down to dihydrolipoic acid, a
more potent antioxidant [95]. Alpha lipoic acid recyles vitamin C,
vitamin E and glutathione. A photoprotective effect of
lipoic/dihydrolipoic acid has been proposed for skin [96].
Flavonoids from fruit extracts had been reported to
diminish acute and chronic skin damages [97]. Apigenin, catechin,
epicatechin, α-glycosylrutin and sylmarin are polyphenolic
compounds and their phenolic groups bestow them with
antioxidative capability. Topical application of polyphenol (2)-
epigallocatechin-3-gallate, the major flavonoid of green tea, before
UVB exposure had resulted in decreased erythema in humans [98].
6.3.2 Sunscreen
Regular use of an effective sunscreen is important in protecting the

skin from UV irradiation and thus minimizing the effect of
photoaging. Chemical sunscreen absorbs UV rays, while physical
sunscreen reflects harmful rays away from the skin [99].
Traditional chemical sunscreens are based on para-aminobenzoic
acid (or its derivatives), cinnamates, salicylates, benzophenones,
dibenzoylmethanes, anthraline derivatives, octocrylene and
homosalate [100]. They act by binding to skin protein and
absorbing UVB photons. Avobenzone is a benzophenone that can
also protect against UVA [100]. Physical sunscreens employ
physical agents to reflect or scatter radiation. Most of them contain
iron, zinc, titanium and bismuth. Zinc oxide and titanium dioxide
are highly reflective. Submicron zinc oxide or titanium dioxide has
the added advantage of transmitting visible light while reflecting
UV radiations resulting in invisible sunblock. A sunscreen

formulation incorporated with activated platelet factor has been
patented [101]. This composition is expected to assist in restoring
damaged skin to its natural condition.
Epigallocatechin-3-gallate (EGCG), an active ingredient in
green tea has been shown to be effective as a sunscreen agent.
Caffeine from coffee and tea have been shown to exhibit inhibitory
effects on UVB- induced carcinogenesis [102].
6.3.3 Growth Factors
Vitamin C and vitamin E are common ingredients in

cosmeceuticals for skin repair. In the recent years, scientists have
looked at growth factors for skin renewal of aged and photoaged
skins. Growth factors are cytokines, which function to regulate cell
growth, development and activation. Cytokines are proteins
produced by various cell types and are important in the
maintenance of general homeostasis. They can act on different cell
types.
Sun-exposed skin undergoes changes similar to a chronic
wound. In the past years, the participation of growth factors in
wound healing has been extensively studied [103]. Tissue repair is
extremely complex and is the result of the interaction of many
cytokines and growth factors working together to re-establish a
homeostatic tissue environment.
Growth factors used in cosmetics are derived from animal
sources or plant sources. They can also be produced synthetically.
Epidermal growth factor is widely incorporated into lotions and
creams. Some products, which contain extracts of placenta and
bovine colostrums, are said to contain Interleukin 1 and
Transforming growth factor (α and β) [103]. However, results
remain sketchy, as it is not known if the concentrations of growth
factors in these products are sufficient to elicit tissue response. One
formulation, TNS Recovery Complex® with Nouricel-MDTM,
contains a concentrated, naturally derived human growth factor
solution containing a mixture of amino acids, vitamins,

antioxidants and several growth factors. In vitro studies with
Nouricel-MDTM resulted in the stimulation of keratinocyte and
fibroblast cell proliferation and stimulation of collagen productions
[104]. Once daily applications of formulated product to the
forearm for four weeks showed a 15-78% improvement in upper
dermal collagen [98]. The application of this product on the face
twice daily for two months demonstrated regenerative effects that
are clinically measurable [73].
6.4 HAIR COSMECEUTICALS
Humans have about 100,000 hairs on their heads. Each hair shaft
has three layers with the cuticle, the outer layer, protecting the two
inner layers. In healthy hair, the layers of the cuticle lie flat,
overlap tightly and reflect light. The inner layers are then well
protected from heat, sun, chlorine and other environmental
stressors. When hair is damaged, the cuticles can be separated and
hair may be dry. As the cuticles don’t protect the two inner layers,
hair can break and look dull.
Humans have direct control on their hair in terms of length,
colour and style. Hair plays a significant role in people’s physical
appearance and self-perception. Problems with hair include oily
hair, dandruff and hair loss (alopecia). Hair care includes caring for
hair quality and scalp care.
Hair cosmetics can be categorized into two, which are those
that work on the exocuticle (shampoo, conditioners, serums, hair
sprays, waxes, gels and mousses) and those that work on the cortex
(hair colour, bleaching agents, straightening and perming agents)
[105].
Shampooing is the most frequent form of hair treatment.
Current shampoo formulations contain ingredients that can treat
specific problems. Extract of yarrow (Azhillea millefolium L), has
been used to treat oily hair. The extract contains less than 0.5% by
weight of polyphenolic derivatives [106]. A hair care formulation

comprising of iodopropynyl butylcarbamate, zinc pyrithione, N-
acyl ethylenediamine triacetate and yarrow extract has been
patented [107]. This formulation is purported to clean the hair and
scalp without damaging the fragile biological equilibrium of scalp
and hair.
Dandruff and seborrheic dermatitis are often mentioned
together. Dandruff is the mildest manifestation of seborrheic
dermatitis. Antifungal therapy for Malassezia, a lipophilic yeast, is
effective in treating most cases of seborrheic dermatitis [108]. One
study used a combination of hydrocortisone and miconazole [109].
Ketoconazole shampoo used twice weekly is very effective against
Malassezia [110]. Zinc pyrithione, an antifungal and antibacterial
agent, has been shown to improve stratum corneum ultrastructure
and return it to normal [111]. Selenium sulfide and bifonazole are
also effective against seborrheic dermatitis [108, 112].
The most common form of alopecia is androgenetic
alopecia (AGA) where the condition is hereditary and it can afflict
both men and women [113]. Various active ingredients have been
used for the treatment of alopecia. Tretinoin, a synthetic retinoid,
has been shown to promote and regulate cell proliferation and
differentiation in epithelium, which are important for hair growth
promotion [114]. Spironolactone is an aldosterone antagonist that
works by stopping binding of natural androgens to receptors.
Topical treatment on animal model showed penetration into skin
and showed some effects at the hair follicle bulbs [115]. Minoxidil
is a hair-growth-inducing agent. Minoxidil shampoo has been
widely used in the treatment of alopecia [116]. Amino acids,
particularly arginine/L-arginine and cysteine/L-cysteine, have been
proposed to play a strong role in hair growth [117]. Saw palmetto
extracts apparently stops or reduces the receptor binding of
androgens. It also locally inhibits 5 alpha reductase and 3
ketosteroid reductase, the enzymes that are involved in converting
testosterone to the more potent androgen dihydrotestosterone
(DHT) [117]. Azelaic acid is a saturated dicarboxylic acid that can
be obtained from wheat, rye and barley. It can act as an antiadrogen

by blocking the activity of 5 alpha reductase [118]. Fullerene
nanomaterials has been reported to increase new hair growth and
produce new hair follicle formation within the dermis [119].
New method or technology has been developed for
improving the texture and softness of the hair. The use of
glycylglycine [120], silicon oil in microemulsion preparation
[121], and use of silicon oil-in-water nanoemulsion [122] has been
used to improve the texture, stability and strength of individual
hair shaft. New hair cosmetic products have been developed to
cleanse hair of detritus, improve cuticular and cortical function,
reduce detangling and improve hair shine [123]. Recently, argan
oil has been incorporated in hair cosmetics and become very
popular in the market [105]. Some oils can penetrate the hair [124]
and fill the gap between the cuticle cells and the oils can enhance
lubrication of the shaft and protect hair from breakage [125].
6.5 NATURAL COSMETICS
As stated before, cosmeceuticals can be natural or synthetic. A

number of cosmeceutical active ingredients, whether natural or
synthetic, in skin care products, sun care products and hair care
products have been reviewed. In this section, the emphasis is on
natural cosmetics. The concept of natural has become the source of
contentious debate as consumers worldwide are more focused on
their health, wellbeing and appearance. Terms as natural, organic,
no artificial preservatives and no animal testing are drawing
formidable attention. At the same time, consumers are becoming
more aware that items marketed as natural are not necessarily all
natural products. Body care labels can be confusing with their long
lists of ingredients that are often impossible to understand. It can
be quite difficult for consumers to determine whether an ingredient
is chemically synthesized or natural.
The natural body care segment includes nine categories:

aromatherapy and body oils, body care kits, sets and travel packs,
cosmetic and beauty aids, deodorants, hair products, oral care,
personal care and first aid, skin care and soap and bath
preparations.
6.5.1 Active Ingredients
The following is a list of some of the natural active ingredients

currently employed in cosmetics products.
6.5.1.1 Papain
Papain is in the dried latex obtained from the papaya fruit (Carica
papaya L). It contains proteolytic (protein digesting) enzyme and
other possible components. Papain is widely used in the
pharmaceutical, food and textile industry. It is a protease that is
most commonly used for food processing applications. It also has
been used for wound healing [126]. In cosmetics, it is used to
exfoliate keratotic skin.
6.5.1.2 Aloe Vera
The aloe plant, being a cactus plant, contains over 75 different

ingredients including vitamins, minerals, enzymes, sugars,
anthraquinones or phenolic compounds, lignin, saponins, sterols,
amino acids and salicylic acid. Currently, the plant is most widely
used in areas of skin care, cosmetics and wound healing [127].
Many biological activities, including anti-viral, anti-bacterial,
laxative, protection against radiation, anti-inflammation and
immunostimulation have been attributed to this plant, in particular,
its polysaccharides. It has been shown to activate macrophages and
accelerate wound healing [128].
6.5.1.3 Hyaluronic Acid
Hyaluronan or hyaluronic acid (HA) is a glycosaminoglycan

polymer prominent in embryogenesis and in tissues undergoing
repair. It is responsible for the water content of skin, where half the
hyaluronan of the body is present [129]. The key molecule
involved in skin moisture is HA with its associated water of
hydration. Understanding the metabolism of HA, its reactions
within skin, and the interactions of HA with other skin components
will facilitate the ability to modulate skin moisture, different from
the empirical attempts that have been used up to now. Many of the
cosmetic preparations than contain HA have a concentration of
0.025% to 0.050%, sufficient to give the preparations a very
smooth and viscous feel.
6.5.1.4 Ceramide
Ceramide is a key intermediate in the biosynthesis of all complex

sphingolipids. Due to its major role in maintaining the water-
retaining properties of the epidermis, ceramide is of great
commercial potential in cosmetics and pharmaceuticals such as
hair and skin care products. Many ceramide-containing products
have already been introduced in the cosmetic market, and the effect
of its application is excellent [130-131].
6.5.2 Formulation Challenges of Natural Cosmetics
Customer usage and storage of cosmetics and skin care is often lax.
Care is not taken in replacing lids and fingers are often used to
remove the cream or foundation from the container. A variety of
infections from yeasts, fungi and bacteria such as pseudomonas,
staphylococcus and streptococcus have been identified in cosmetic
preparations. Infections from microorganisms in cosmetics have
also been related to expiry of usable shelf life and extreme
temperature variation during storage.
The presence of preservatives in cosmetic products is

obviously necessary. Contamination of formulations can lead to the
separation of emulsions, product discolouration, the formation of
gasses and odours, as well as the infection of the skin of the users.
However, many preservatives have the potential to cause allergic
reactions on sensitive skins. The more preservatives in a product,
the more likely the formula will cause a sensitivity effect. Some
ingredients can cause allergies in susceptible people, including
dermatitis and other side effects. There are two types of
preservatives that can be categorized based on their source of
origin which are artificial preservatives (a group of synthetic
chemical substances) and natural preservatives (chemical
constituents extracted from natural sources [132].
At the present time, parabens, (methylparaben, ethylparaben
and butylparaben etc) are the most commonly found cosmetic
preservatives.
For natural cosmetics the biggest formulation challenge is
using a natural preservative that is as efficacious as a chemical
preservative but without the associated sensitizing effect. These
natural preservatives can be categorized into four types which are
plant derived (herbs and spices), animal derived (lard), certain
microbes (bacteriocins) and certain antimicrobial (lysozyme,
avidin, etc) [132]. They can also be categorized based on their
mode of action which are antimicrobials (inhibit the growth of
bacteria, yeast, molds or fungi) and antioxidants (inhibit the
oxidation of the product) [133-135]. Some of the potential natural
preservatives are reviewed here. However, before that, the
following are the commonly used chemical preservatives in
cosmetics product.
6.5.2.1 Paraben
Parabens are widely used as cosmetic preservatives in a large

variety of products, including face, body and hand creams, lotion
and moisturizers. Paraben are found in all type of formulations and
have a use in over 13, 200 formulations [136]. Paraben

preservatives are listed under multiple names and are used to
preserve the majority of cosmetics on the market today, not only to
prevent the growth of bacteria and fungi but also to promote the
abnormally long shelf-life of products. Parabens are synthetic
preservatives that have been in use since the 1920s as user friendly
preservatives (anti-bacterial and anti-fungal) which means that they
work within a formula to prevent the growth of multiple possible
contaminants such as bacteria, yeast, mold and fungi. They can be
found in approximately 75-90 percent of cosmetics such as make-
up, lotion, deodorants and shampoos. Paraben are reported to cause
contact dermatitis reactions in some individuals on cutaneous
exposure [137].
Paraben preservatives have also been identified as
endocrine disruptors. Paraben preservatives are believed to mimic
the female hormone estrogen when introduced into the body. New
cosmetic companies which are more focused on offering natural
and organic products have made their ‘no paraben’ policy a
platform issue. This means there are a wide variety of paraben-free
cosmetic products, which are mostly now available for purchase in
health food stores and on the internet. To date, among the studies
that have been done world-wide, paraben preservatives have been
linked to breast cancer and have been labeled as a possible
endocrine disruptor that might have specific damaging
consequences for young children and those with ongoing exposure.
6.5.2.2 Formaldehyde
This is an inexpensive and effective preservative that is widely

used in cosmetics as a disinfectant, germicide, fungicide and de-
foamer. It has been estimated that between 4-8% of the general
population may have become sensitive to this popular preservative.
In Japan and Sweden the used of formaldehyde in cosmetic
products is prohibited because of safety issues.
6.5.2.3 Quartenium-15
Quaternium-15 is a preservative found in many cosmetics. It is a

water soluble anti-microbial agent that has been proven active
against bacteria, but less active against yeasts. It is a formaldehyde
releaser, and may be a major cause of dermatitis from
preservatives. Those who are allergic to formaldehyde can
potentially have problems with this ingredient. It has also recently
been found that quaternium-15 can react in the body with other
chemicals to produce nitrosamines. However, it is not known
whether enough Q-15 can be absorbed through the skin for the
carcinogen producing action to occur.
6.5.2.4 Euxyl K 400
The newest preservative system found in cosmetics, Euxyl K 400,

is a combination of Phenoxyethanol and
Methyldibromoglutaronitrile. Euxyl K 400 is a preservative for
cosmetics and toiletries. In The Netherlands, Italy, and Germany,
the prevalence of allergy to Euxyl K 400 has risen in the past 4
years. Euxyl K 400 is the culprit in about 2% to 4% of patients
suspected of having contact dermatitis. The allergenic ingredient is
nearly always methyldibromoglutaronitrile. Beside Euxyl K 400,
other common names for this preservative are shown below:
(1) 1, 2- dibromo-2, 4-dicyanobutane

(2) 1,2-Dibromodicyanobutane
(3) 2-phenoxyethanol
(4) Dibromodicyanobutane
(5) Merquat 2200
(6) Tektamer 38
(7) Methyldibromoglutaronitrile
(8) Tektamer 38
(9) Merquat 2200
Methyldibromoglutaronitrile (MDBGN) was introduced to

the European market in 1985, as a preservative for cosmetics,
toiletries and industrial products. The dermatitis caused by
MDBGN can affect not only the head and neck region but also the
perianal skin or hands [138].
6.5.3 Alternative Preservatives
Although chemical preservatives do extend the longevity of the

products and help keep them free from bacteria, the preservatives
themselves are often unhealthy. The use of a natural preservative in
formulas that are basically inert (like most powder mineral
cosmetics) or have an oil base and no water (like lipstick or liners)
are demanding. In products such as these, a plant extract or
essential oil with anti-microbial and anti-oxidant properties such as
grapefruit seed extract, grape seed extract or tocopherol (vitamin
E) can be used as an effective preservative system. Surprisingly,
most natural substances are not active against the most threatening
microbes, pseudomonas because pseudomonas itself is a plant
pathogen. The usage of essential oils in the formulation, require
very high concentrations to make the products effective.
Formulating anhydrous products is another way to
eliminate the need for chemical antimicrobial preservatives. Bar
soaps typically do not require an antimicrobial but stay fresher
when an antioxidant is used. In addition, natural cosmetic products
can be stored in smaller container to be used for short period of
time because natural products will not stay fresh for as long as
commercial products do.
6.5.3.1 Antioxidants
There is a recent increase in serious research on the commercial

application of radical scavengers and flavonoids as a beneficial
anti-ageing and photoprotection of ingredients in cosmetic
products [139]. An anti-oxidant is a preservative that reduces the
rate of oxidation in oils that oxidize quickly. Oxidation is a

chemical process that occurs when oils or other natural ingredients
are exposed to oxygen. Anti-oxidants extend the shelf life of the
formulation and the end products by reducing the rate of oxidation.
The usage of an antioxidant in any formulation, which contains
fragile oils such as sweet almond, hemp, avocado, flax or evening
primerose will preserve the products.
6.5.3.2 T-50 Vitamin E Oil (Tocopherol)
Vitamin E contains natural antioxidants, which extend the life of

products. Gamma tocopherol, a component of Vitamin E, is a great
antioxidant for protecting cosmetic formulations. T-50 has a larger
amount of gamma tocopherols than other forms of Vitamin E oil.
While the alpha tocopherol in the 250, 1000, and 1400 IU/g oils is
wonderful as an in vitro antioxidant, studies show that gamma
tocopherol in the Vitamin E T-50 oil is a better antioxidant for oils
or lipids in cosmetic formulations. T-50 has a higher content of
gamma tocopherols and can be used at a rate of 0.4% or 400 ppm
to adequately protect the oils.
6.5.3.3 Grape Seed Extract
Grape fruit Seed Extract (GSE) is a citrus seed based anti-

microbial used as a preservative in skin care products. It is made
with the extracts of citrus seeds and pulp. It is blended with
vegetable glycerin to make it non-irritating to the skin and mucous
membranes when used in formulations. The concentration of
grapefruit seed extract in cosmetic formulation is at 0.5 to 1% to
preserve most formulations. However, at 2% of concentration the
formulation will create anti-bacterial creams, salves, rinses and
soaps.
6.5.3.4 Usnic Acid
Usnic acid is uniquely found in lichens, and is especially abundant

in genera such as Alectoria, Cladonia, Usnea, Lacanora, Ramalina
and Evernia. Many lichens and extracts containing usnic acid have
been utilized for medical, perfumery, cosmetics and as ecological
applications. As a pure substance usnic acid has been formulated in
creams, toothpaste, mouthwash, deodorants and sunscreen
products as preservatives. Usnic acid has been shown to exhibit
antiviral, antiprotozoal, antiproliferative, anti-inflammatory and
analgesic activity [140]. Extracts of U. barbata have been used as a
source of usnic acid in modern-day cosmetic and pharmaceutical
preparations.
6.5.3.5 Essential Oil
Essential oils (tea tree, thyme, lemon grass, oregano, rosemary,

lavender, etc) can be obtained through water or steam distillation,
solvent extraction, expression under pressure, supercritical fluid or
subcritical water extractions [167]. There are more than 3000
essential oils used in the flavour and cosmetics industries [141].
Previous studies have shown that the antimicrobial effect of
essential oil depends on content, concentration and interactions
between the main active ingredients. These essential oils are
effective in controlling bacteria activity through membrane
disruption by their lipophilic components such as terpenes and
terpenoids which can pass through cell walls and cytoplasmic
membranes [141] and effective in controlling fungi through
cytoplasmic membrane lesion by the disruption of sterol
biosynthesis [142-144]. Even though the essential oils are
considered safe preservatives but some of them may cause risk of
irritation, sensitization, phototoxicity or allergic reactions [145].
6.6 COSMETICS AND TECHNOLOGY
Another hot issue within the cosmetics industry is the application

of technology. Today, as technology becomes more sophisticated
and readily available, cosmetics and technology have become more
inextricably interconnected. Biotechnology has impacted the
cosmetic industry like never before in terms of development of
ingredients and cosmetic testing. The cosmetics industry has
witnessed an explosion in the use of ingredients that are
biologically derived such as marine based products and plant based
products. Ingredients that originate from fermentation processes
are also becoming more common. Safety testing of cosmetics
ingredient has also been revolutionized. Efforts to move away from
animal testing leads to the use of skin culture to produce skin
equivalents. To effectively deliver the ingredients to the skin,
delivery systems are becoming more sophisticated with
nanotechnology coming to the forefront.
6.6.1 Biotechnology and Cosmetic Ingredients
More cosmetics ingredients have been developed using

biotechnology. Recombinant proteins, growth factors and
cytokines, traditionally used for drug development, are now
gaining entry into the cosmetic industry. Some ingredients
produced using biotechnology are listed below. This list is in no
way exhaustive.
Hyaluronan (HA), a key factor in skin moisture, is one
ingredient that is produced using biotechnology. The advantage of
using HA in cosmetic formulations was recognized soon after its
discovery, however difficulty in producing HA in large amount
limited its use in cosmetics. Previously, HA was derived from
rooster combs [139]. Advances in genetic engineering and
biotechnology have made mass production of HA possible.
Bacteria with enhanced HA production through the amplification
of the HA synthase (HAS) genes have been engineered [129].
Production of HA using fermentation process reduces the price of

HA. This made HA available for cosmetic products.
Kojic acid is a depigmentation agent. Kojic means ferment
in Japanese and it had been used to brew Sake from rice. Kojic
acid is a fungal metabolic product. Pure kojic acid can be produced
from glucose by fermentation [55].
Growth factors are another class of cosmetic ingredients
that can be produced using biotechnology. They can also be
derived from animals and plants. Epidermal growth factor can be
derived from yeasts or recombinant genetic technologies [103].
Heat shock proteins (Hsp) represent a family of proteins,
which help maintain cell integrity after the cell is exposed to stress.
Hsp70 is of interest to the cosmetics industry. For skincare, the
strategy is either to induce Hsp70 or to provide Hsp70 from
another source. The synthetic Hsp70 is usually produced from
yeast using biotechnology [146]. Ectoine is one of the organic low
molecular weight compounds produced by halophilic
microorganisms under hyperosmotic stress [147]. It can protect
enzymes, membranes and whole cells against stresses caused by
exposure to salt, heating, freezing and desiccation [148]. The
biotechnological commercial production of ectoine, or bacterial
milking, is carried out using the halophilic gram negative
bacterium Halomonas elongata [149]. Ectoine can also induce the
expression of the heat shock proteins Hsp70 and Hsp70B’ in
human keratinocytes [150]. Ectoine has now been used as a
moisturizer in cosmetics and skin care products [151].
6.6.2 Tissue Enginereed Skins
For reasons of safety, ingredients and product formulation need to

be tested for irritant potentials. Skin irritation is one of the most
common adverse effects of cutaneous inflammatory reactions in
humans. Traditionally, animal models are used. The Draize skin
irritation tests employ patches on rabbit skin [152]. However,
testing on animals will cause them pain and discomfort.
Furthermore, the results might not be predictive for those found in

humans. Social and political pressures against animal testing are
increasing, resulting in the search of alternative methods of testing.
A variety of cell-based methods have been developed and
used for the assessment of skin irritants. Cell models include
monolayer cultures of keratinocytes; mutilayered (3D) cultures of
skin cells that provide a barrier function similar to the surface of
the skin; and co-culture models where two or more of the types of
cells on the skin are represented [153].
The 3D skin models usually consist of human cells grown
on a membrane at the air-liquid interface [154]. This culture
method will induce the cells to grow in multilayers. Several 3D
models are commercially available such as EpiDermTM (MatTek
Corporation, MA, US), EPISKINTM (Skinethic, Nice, France) and
RealSkinTM (Skinethic, Nice, France).
6.6.3 Plant Tissue Culture
Plant tissue culture in the osmetic field is not as widespread as in

the pharmaceutical industry [66]. Explant is the plant tissue culture
that is used to initiate a plant cell culture and can be used with
different efficiency depending on the plant species [67]. Callus is a
mass of cells that is resulted when explant expands their volume,
start to divide and differentiate from the result of wounding [67].
Hydrosoluble (water soluble) and liposoluble (oil soluble) extracts
may be derived from the same plant cell culture. Wild red
raspberry (Rubus ideaus) have been cultured in a reactor to
produce extracts for use in cosmetics [68]. The water soluble
compounds (amino acid, glucides, flavonoids, phenolic acid) have
high antioxidant property which can protect skin cells from
oxidative stress [69]. Meanwhile, liposoluble compounds
(vitamins, tocopherols, fatty acids) [155] were shown to exhibit
high anti-inflammatory activity [68]. A plant cell wall from
woodland tobacco (Nicotiana sylvestris) cell cultures was shown to
have strong anti-ageing properties [156].
6.6.4 Cosmetic Delivery Systems
Cosmetic ingredients must be delivered to the site of action for

them to work effectively. Most ingredients interact in the lower
part of stratum corneum or modulate the functions of the epidermal
or dermal cells. To facilitate transport through the skin barrier, the
ingredients are integrated into appropriate cosmetic delivery
systems. The development of cosmetic delivery systems is mostly
influenced by development of new synthetic surfactants and the
knowledge of the mechanism involved in percutaneous absorption
[157].
Traditionally, cosmetic leave-on formulations are usually
complex emulsions of water dispersed in oil (w/o) or oil dispersed
in water (o/w). Usually cosmetic day care products are o/w
emulsions and night creams are w/o emulsions [158]. Today, new
galenical formulations have been designed.
6.6.4.1 Nanodispersed Systems
Nanodispersed systems include liposomes, nanocapsules,

nanoemulsions and lipid nanoparticles. They are mostly lipid based
and even though they are mostly used as delivery systems, their
own structure may affect skin hydration.
Liposomes were introduced by Bangham et al. [159] in
1960s. They are self-assembled colloidal particles produced by
dispersion of naturally occurring phospholipids in water. The
envelope is formed with mono- or multilamellar bilayers and the
core is aqueous. Liposomes can encapsulate water-soluble
ingredient in their core and hydrophobic ingredients may be
incorporated within the bilayer membranes. Liposomes can
interact with cutaneous cells due to the similarity of their structure
with cellular membranes. Niosomes are similar to liposomes but
they are formed using synthetic non-ionic surfactants.
Nanocapsules are core material enclosed in nano-thickness
shell. The core material is usually liquid. Their main applications
are to protect the sensitive materials from the environment and to

get an active ingredient to a specific location and release it under
certain conditions.
Nanoemulsions are o/w emulsions with an average droplet
size ranging from 100 to 500 nm. They contain 10 to 20% of oil
stabilized by non-ionic surfactants which are usually
phospholipids. They have a liquid lipophilic core. Nanoemulsions
have been shown to increase cutaneous penetration of active
ingredient and reduce transepidermal water loss [160].
Solid lipid nanoparticles (SLN) are droplets made by solid
lipids. Their sizes range from 50 to 1000 nm. There are mainly
three structures: homogeneous matrix, drug-enriched shell and
drug-enriched core. SLN can be very efficient in promoting
penetration into stratum corneum [161].
6.6.4.2 Multiple Emulsions
Multiple emulsions are complex systems that combine both o/w

systems and w/o systems in one vehicle. w/o/w system is the
dispersion of aqueous droplet embedded in oil droplet and this oil
droplet is dispersed in an aqueous phase. There are three types of
multiple emulsions: each oil droplet contains one large internal
water droplet, each oil droplet contains several water droplets and
each oil droplet contains lots of internal water droplets [162]. With
multiple emulsions, different incompatible water-soluble
ingredients and oily soluble additives can be incorporated in one
vehicle. Controlled delivery can be achieved by regulating droplet
breakdown. These systems can also provide good hydration as they
can contain high percentages of the oily phase.
6.6.4.3 Microemulsions
Microemulsions are transparent mixtures of water, oil and

surfactants. They are thermodynamically stable and optically
isotropic [163]. Microemulsions are spontaneously produced in a
narrow range of oil-water-surfactant composition. They are

dynamic systems with fluctuating interfaces. For cosmetic
products, they are either in liquid or gel-like form. Microemulsions
are usually found in skin care gels and lotions, hair treatment
formulation and gel type antiperspirant and deodorant.
One drawback to this system is that its formation requires
the use of high concentrations of surfactants and co-surfactants.
This may result in problems such skin irritancy and solubilization
of essential components of stratum corneum. Nowadays, these
issues have been the focus of many research efforts on
microemulsions [164].
6.7 FUTURE DIRECTIONS
Cosmeceuticals emphasize the functional aspects of cosmetic

products. The cosmeceutical market, particularly its natural
segment, with its promise to deliver effective cosmetics safely, will
continue to expand. However, there are still some issues that have
to be considered within the industry.
First and foremost, claims of efficacy have to be backed up.
Proof of efficacy is becoming important now more than ever. Even
though most cosmeceutical ingredients have scientific merits;
questions still arise whether or not their concentrations in cosmetic
formulations render them effective. Nowadays, consumers are very
savvy and discriminative. With the wide variety of choices
available, consumers will discontinue use of ineffective products.
Consumers are also more natural consciousness. They are
demanding the use of more and more natural ingredients as they
have been more exposed to the negative press about chemicals and
toxic substances. This has prompted the cosmetic companies to
increase the uses of natural ingredients in their products, even if
only for press purposes. Thus, natural products and extracts will
continue to replace chemical ingredients as much as possible. In
addition, animal sources will continue to be replaced by plant and
fermentation sources.
Holistic therapy will influence skin care developments.
Ingredients that can promote homeostasis will be more favoured.
Fungi such as chaga, reishi and elm oysters are alleged to boost
vitality, benefit the immune system and promote skin resilience
and tautness.
The mineral-based cosmetics are also very demanding
today. The idea behind using natural minerals is that they safely
and efficiently deliver a natural look while leaving out the harmful
effects of chemicals. Minerals are light, non-abrasive, and often
contain other beneficial qualities that help the skin stay healthy.
Perhaps the most important quality related to mineral-based
cosmetics is the natural sun protection. Unlike regular sunscreen,
which uses mostly chemical sun blockers, minerals are a natural
barrier that doesn’t require constant re-application or rinsing
afterwards.
Delivery systems will continue to be more complex.
Delivery systems with effective cutaneous penetration that offer
controlled release of active ingredients will be more sought after.
Nanotechnology will continue to dominate the research and
development of effective cosmetics delivery systems. It will
elevate the development of skin care products and cosmetics to
another level. In the cosmetic arena it is believed that the smaller
particles are more readily absorbed into the skin.
With the reduction in the ozone layer, UV exposure is more
intense. The threat of photoaging is more serious. Thus, sunscreen
actives are now more increasingly present in daily wear products.
New cosmeceutical products will offer broad spectrum UV
coverage, higher sun protection factors and more potent anti-
oxidants.
Travel is also expected to impact the cosmetics industry.
People are constantly on the move, whether work related or for
leisure. Travel packs are well-liked but monodose product will
grow in popularity. They are more convenient for the on-the-go
consumers.
Regulation has always been an issue with the

cosmeceuticals industry. In US and Europe, topical products are
classified as either drugs or cosmetics. In Japan, there is another
category called quasidrugs, which covers cosmetics products with
pharmacological action [4]. As such, cosmeceuticals are not
regulated in US and Europe. However, the FDA has assured the
safety of cosmetics ingredients through the Cosmetic Ingredient
Review program [165]. On the other hand, many of the topical
products corresponding to cosmeceuticals fall into the category of
quasidrugs in Japan. With the exception of some such as anti-
wrinkle products, the manufacturers of quasidrugs are required to
obtain government approvals before marketing. Approval of a
product is contingent upon judgement of Japan’s Ministry of
Health, Labour and Welfare.
Now the category of an active ingredient differs from one
country to the other. In the USA, antiperspirants, antidandruff
shampoos and sunscreens are regulated as drugs and in Europe
they are sold as cosmetics [141]. In Japan, if the action of an
antidandruff shampoo on the human body is mild, it will be
categorized as a quasidrug. Harmonization of cosmetics and drug
products regulation particularly between the USA, European Union
and Japan might be expected in the future. Harmonization will
prevent the current situation where some products are registered as
drugs in one country but as cosmetics or cosmeceuticals in other
countries.
REFERENCE
[1] Barbalova, I. 2011. “Global Beauty and Personal Care: The

Year in Review and Winning Strategies for The Future” (online).
Retrieved from http://www.incosmetics.com/RXUK/RXUK
InCosmetics/documents/IC11EuromonitorIntGlobalBeautyAndPer
sonalCare (Accessed 15 June 2014).
[2] U.S. Food and Drug Administration Centre for Food Safety and
Applied Nutrition. 2002. “CFSAN/Office of Cosmetics and Colors

Fact Sheet: Is it a Cosmetic, a drug or both? (or it is Soap?)”
(online). Retrieved from http://www.cfsan.fda.gov/dms/cos-
218.html (Accessed 15 June 2014).
[3] The Council of The European Communities Official Journal of
the European Commission – L series 151. “Directive 93/35/EEC”
(online). Retrieved from http://eur-lex.europa.eu/legal-
content/EN/NOT/?uri=CELEX:31993L0035&qid=1458440341871
(Accessed 15 June 2014).
[4] Editorial supervision by Pharmaceuticals and Cosmetics
Division, Pharmaceutical Affairs Bureau, Ministry of Health and
Welfare. 1992. Guide to Quasi-drug and Cosmetic Regulations in
Japan. Tokyo: Yakuji Nippo.
[5] Elsner, P. and H. I. Maibach. 2000. Cosmeceuticals: Drugs vs
Cosmetics. New York: Marcel Dekker.
[6] Millikan, L. E. 2001. “Cosmetology, Cosmetics,
Cosmeceuticals: Definitions and Regulations.” Clinics in
Dermatology, 19(4): 371-374.
[7] Dooley, T. P. 1997. “Is There Room for A Moderate
Regulatory Oversight?” in. W. Hori (ed.). Drug Discovery
Approaches for Developing Cosmeceuticals: Advanced Skincare
and Cosmetics Products. Southborough: IBC Library Series.
[8] Tortora, G. J. and S. R Grabowski. 1993. Principles of
Anatomy and Physiology. New York: Harper Collins College
Publisher.
[9] Wertz, P. W., M. C. Miethke, S. A. Long, J. S. Strauss, and D.
T. Downing. 1985. “The Composition of Ceramides in Human
Stratum Corneum and from Comedones.” Journal of Investigative
Dermatology, 84(5): 410-412.
[10] Elias, P. M. and D. S. Friend. 1975. “The Permeability Barrier
in Mammalian Epidermis.” The Journal of Cell Biology, 65(1):
180-191.
[11] Harding, C. R., A. Watkinson, A. V. Rawlings, and I. R.
Scott. 2000. “Review Article: Dry Skin, Moisturization and
Corneodesmolysis.” International Journal of Cosmetic Science,
22(1): 21-52.
[12] Lintner, K., C. Mas-Chamberlin, P. Mondon, F. Lamy, and O.
Peschard. 2005. “Cutaneous Barrier Repair” in. P. Elsner and H. I.
Maibach (eds.). Cosmeceuticals and Active Cosmetics: Drugs
Versus Cosmetics, Cosmetics Science and Technology Series.
Boca Raton: Taylor & Francis.
[13] Loden, M. 2005. “Moisturizers” in P. Elsner and H. I.
Versus Cosmetics, Cosmetics Science and Technology Series. Boca
Raton: Taylor & Francis.
[14] Middleton, J. 1974. “Development of A Skin Cream Designed
to Reduce Dry and Flaky Skin.” J. Soc. Cosmet. Chem., 25(8):
519-534.
[15] Silverman, A. K., C. N. Ellis, and J. J. Voorhees. 1987.
“Hypervitaminosis A Syndrome: A Paradigm of Retinoid Side
Effects.” Journal of the American Academy of Dermatology, 16(5):
1027-1039.
[16] Chew, A., S. J. Bashir, and H. I Maibach. 2005. “Topical
Retinoids” in P. Elsner and H. I. Maibach (eds.). Cosmeceuticals
and Active Cosmetics: Drugs Versus Cosmetics, Cosmetics
Science and Technology Series. Boca Raton: Taylor & Francis.
[17] Goodman, D. S. 1984. “Vitamin A and Retinoids in Health
and Disease.” New England Journal of Medicine, 310(16): 1023-
1031.
[18] Griffiths, C. E. 1999. “Drug Treatment of Photoaged Skin.”
Drugs & Aging, 14(4): 289-301.
[19] Ellis, C. N., J. S. Weiss, T. A. Hamilton, J. T. Headington, A.
S. Zelickson, and J. J. Voorhees. 1990. “Sustained Improvement
with Prolonged Topical Tretinoin (Retinoic Acid) for Photoaged
Skin.” Journal of the American Academy of Dermatology, 23(4):
629-637.
[20] Misiewicz, J., E. Sendagorta, A. Golebiowska, B. Lorenc, B.
M. Czametzki, and S. Jablonska. 1991. “Topical Treatment of
Multiple Actinic Keratoses If The Face with Arotinoid Methyl
Sulfone (Ro 14-976) Cream versus Tretinoin Cream: A Double
Blind, Comparative Study.” Journal of the American Academy of

Dermatology, 24(3): 448-451.
[21] Kligman, A. M. 1989. “Guidelines for The Use of Topical
Tretinoin (Retin-A) for Photoaged Skin.” Journal of the American
Academy of Dermatology, 21(3): 650-654.
[22] Kang, S., E. A. Duell, G. J. Fisher, S. C. Datta, Z. Q. Wang,
A. P. Reddy, A. Tavakkol, Y. Y. Jong, C. E. Griffiths, J. T. Elder,
and J. J. Voorhees. 1995. “Application of Retinol to Human Skin
In Vivo Induces Epidermal Hyperplasia and Cellular Retinoid
Binding Protein Characteristic of Retinoic Acid, but Without
Measurable Retinoic Acid Levels or Irritation.” Journal of
Investigative Dermatology, 105(4): 549-556.
[23] Duell, E. A., F. Derguini, S. Kang, J. T. Elder, and J. J.
Voorhees. 1996. “Extraction of Human Epidermis Treated with
Retinol Yields Retro-retinoids in Addition to Free Retinol and
Retinyl Esters,” Journal of Investigative Dermatology, 107(2):
178-182.
[24] Hodam, J. R. and K. E. Creek. 1998. “Comparison of The
Metabolism of Retinol Delivered to Human Keratinocytes Either
Bound to Serum Retinol-binding Protein or Added Directly to The
Culture Medium.” Exp. Cell Res., 238 (1): 257-264.
[25] Bailly, J., M. Cretaz, M. H. Schifflers and J. P. Marty. 1998.
“In Vitro Metabolisms by Human Skin and Fibroblasts of Retinol,
Retinal and Retinoic Acid.” Exp. Dermatol., 7(1): 27-34.
[26] Uhoda, E., C. Pierard-Franchimont, L. Petit and G. E. Pierard.
2005. “Hydroxyacids” in P. Elsner and H. I. Maibach (eds.).
Cosmeceuticals and Active Cosmetics: Drugs Versus Cosmetics,
Cosmetics Science and Technology Series. Boca Raton: Taylor &
Francis.
[27] Huber, C., E. Christophers. 1977. “Keratolytic Effect of
Salicylic Acid.” Archives of Dermatological Research, 257(3):
293-298.
[28] Rubin, M. G. 1994. “Therapeutics: Personal Practice. The
Clinical Use of Alpha Hydroxy Acids.” Australasian Journal of
Dermatology, 35(1): 29-33.
[29] Murad, H., A. T. Shamban, and P. S. Premo. 1995. “The Use

of Glycolic Acid as A Peeling Agent.” Dermatologic Clinics,
13(2): 285-307.
[30] Leyden, J. J. and A. R. Shalita. 1986. “Rational Therapy for
Acne Vulgaris: An Update on Topical Treatment, J. Am. Acad.
Dermatol., 15(4): 907-914.
[31] Smith, W. P. 1994. “Hydroxy Acids and Skin Aging.”
Cosmetics and Toiletries, 109(9): 41-44.
[32] Bernstein, E. F. and J. Uitto. 1995. “Connective Tissue
Alterations in Photoaged Skin and The Effects of Alpha-hydroxy
Acids.” J. Geriatr. Dermatol., 3(Supplement A): 7A-18A.
[33] Lavker, R. M., K. Kaidbey, J. J. Leyden. 1992. “Effects of
Topical Ammonium Lactate on Cutaneous Atrophy from A Potent
Topical Corticosteroid.” J. Am. Acad. Dermatol., 26(4): 535-544.
[34] Burns, R. L., P. L. Prevost-Blank, M. A. Lawry, T. B. Lawry,
D. T. Faria, and D. P. Fivenson. 1997. “Glycolic Acid Peels for
Post Inflammatory Hyperpigmentation in Black Patients.”
Dermatologic Surgery, 23(3): 171-175.
[35] Elson, M. L. 1992. “The Utilization of Glycolic Acid in
Photoaging.” Cosmet. Dermatol., 5(1): 12-15.
[36] Hermitte, R. 1992. “Aged Skin, Retinoids and Alpha Hydroxy
Acids.” Cosmetics and Toiletries, 107(7): 63-67.
[37] U.S. Food and Drug Administration Centre for Food Safety
and Applied Nutrition Office of Cosmetics and Colors Fact Sheet.
1997. “Alpha Hydroxy Acid in Cosmetics” (online). Retrieved
from http://vm.cfsan.fda.gov/~dms/cos-aha.html. (Accessed 2 July
2014).
[38] Khaiat, A. 2005. “Botanical Extracts” in P. Elsner and H. I.
[39] Leung, A. Y. 1980. Encyclopedia of Common Ingredients
Used in Food, Drugs and Cosmetics. New York: Wiley.
[40] Lee, O. S., H. H. Kang, and S. H. Han. 1997. “Oriental Herbs
in Cosmetics: Plant Extracts are Reviewed for Their Potential as
Cosmetic Ingredients.” Cosmetic and Toiletries, 112(1): 57-64.

[41] Ito, M., H. Tanaka, and H. Kojima. 1994. “Chouji and
Gennoshouko Extracts as A Useful Scavenger of Reactive Oxygen
Species for Cosmetics.” Fragrance Journal, 22: 38-42.
[42] Loden, M. and A. C. Andersson. 1996. “Effect of Topically
Applied Lipids on The Surfactant-irritated Skin.” British Journal
of Dermatology, 134(2): 215-220.
[43] Adjei, A. A., K. Yamauchi, Y. Nakasone, M. Konoshi, and S.
Yamamoto. 1994. “Arginine Supplemented Diets Inhibit
Endotoxin-induced Bacterial Translocation in Mice.” Nutrition, 11
(4): 371-374.
[44] Welhourne, T. C. 1995. “Increased Bicarbonate and Growth
Hormone After An Oral Glutamine Load.” The American Journal
of Clinical Nutrition, 61(5): 1058-1061.
[45] Hattori, A., H. Migitakia, and R. J. Reiter. 1995.
“Identification of MSH in Plants and Its Effects on Plasma
Melatonin Levels and Binding to Melatonin Receptors in
Vertebrates.” Biochem. Mol. Biol. Int., 35(3): 627-634.
[46] Lassus, A. 1993. “Colloidal Silicic Acid for Oral and Topical
Treatment of Aged Skin, Fragile Hair and Brittle Nails in
Females.” J. Int. Med. Res., 21(4): 209-215.
[47] Sakamoto, K. 2005. “Amino Acids and Derivatives” in P.
Elsner and H. I. Maibach (eds.). Cosmeceuticals and Active
Cosmetics: Drugs Versus Cosmetics, Cosmetics Science and
Technology Series. Boca Raton: Taylor & Francis.
[48] Koyoma, J., J. Nakanishi, Y. Masuda, J. Sato, J. Nomura, Y.
Suzuki, and Y. Nakayama. 1996. “The Mechanism of
Desquamation in the Stratum Corneum and Its Relevance to Skin
Care.” Proceedings of the 19th IFSCC Congress.
[49] Rawlings, A. V., I. R. Scott, C. R. Harding, and P. A. Bowser.
1994. “Stratum Corneum Moisturization at The Molecular Level.”
J. Invest. Dermatol., 103(5): 731-741.
[50] MacKay, D. J. and A. L. Miller. 2003. “Nutritional Support
for Wound Healing.” Alternative Medicine Review, 8(4): 359-378.
[51] Sakamoto, K. 1984. “Development of Two New Moisturizing
Ingredients.” Cosmetics and Toiletries, 99(3): 109-110.

[52] Ishii, H., N. Mikami, and K. Sakamoto. 1996. “Lipo-amino
Acid Cholesteryl Derivatives Promote Recovery Effect for
Damaged Skin.” Journal of The Society of Cosmetic
Chemists, 47(6): 351-362.
[53] Bissett, D. L., R. Chatterjee, and D. P. Hannon. “Chronic
Ultraviolet Radiation-induced Increase in Skin Iron and
The Photoprotective Effect of Topically Applied Iron Chelators.”
Photochemistry and Photobiology, 54(2): 215-223.
[54] Kitazawa, M. and K. Iwasaki. 1996. “Suppression of Iron
Catalyzed Free Radical Generation by Iron Tyrosinate Protein
Models.” Biochemical and Biophysical Research Communications,
220(1): 36-41.
[55] Nakayama, H., E. Tamotsu, N. Satoh and T. Jinnai. 2005.
“Depigmentation Agents” in P. Elsner and H. I. Maibach (eds.).
Francis.
[56] Sato, N. 1987. “Endocrine Environment in Adult Females
with Chloasma.” The Japanese Journal of Dermatology, 97(8):
937-943.
[57] Palumbo, A., M. d’Ischia, G. Misuraca, and G. Prota. 1991.
“Mechanism of Inhibition of Melanogenesis by Hydroquinone.”
Biochimica et Biophysica Acta (BBA)-General Subjects, 1073(1):
85-90.
[58] Maeda, K. and M. Fukoda. 1991. “In vitro Effectiveness of
Several Whitening Cosmetic Components in Human
Melanocytes.” J. Soc. Cosmet. Chem., 42(2): 261-268.
[59] Jimbow, K. 1991. “N-acetyl-4-w-cyteaminylphenol as A New
Type of Depigmenting Agent for The Melanoderma of Patients
with Melisma.” Arch. Dermatol., 127(10): 1528-1534.
[60] M. Jimbow, H. Marusyk and K. Jimbow. 1995. “The In Vivo
Melanocytotoxicity and Depigmenting Potency of N-2,4-
acetoxylphenyl Thioethyl Acetamide in The Skin and Hair.” Br. J.
Dermatol., 133(4): 526-536.
[61] Kameyama, K., C. Sakai, S. Kondoh, K. Yonemoto, S.

Nishiyama, M. Tagawa, T. Murata, T. Ohnuma, J. Quigley, A.
Dorsky, and D. Bucks. 1996. “Inhibitory Effect of Magnesium L-
Ascorbyl-2-Phosphate (VC-PMG) on Melanogenesis In Vitro and
In Vivo.” Journal of The American Academy of
[62] Breathnach, A. S. 1996. “Melanin Hyperpigmentation of Skin:
Melasma, Topical Treatment with Azelaic Acid and Other
Therapies.” Cutis, 57(1): 36-45.
[63] Nakayama, H., H. Watanabe, K. Nishioka, R. Hayakawa, and
Y. Higa. 1982. “Treatment of Chloasma with Kojic Acid Cream.”
Rinsho Hifuka, 36: 715-722.
[64] Garcia, A., and J. E. Fulton. 1996. “The Combination of
Glycolic Acid and Hydroquinone or Kojic Acid for The Treatment
of Melasma and Related Conditions.” Dermatologic
Surgery, 22(5): 443-447.
[65] Kang, W. H., S. C. Chun, and S. Lee. 1998. “Intermittent
Therapy for Melasma in Asian Patients with Combined Topical
Agents (Retinoic Acid, Hydroquinone and Hydrocortisone):
Clinical and Histological Studies.” The Journal of
Dermatology, 25(9): 587-596.
[66] Barbulova, A., F. Apone, and G. Colucci. 2014. “Plant Cell
Cultures as Source of Cosmetics Active Ingredients.” Cosmetics,
1(2): 94-104.
[67] Chermahini, S. H., F. A. A. Majid, M. Sarmidi. 2011.
“Cosmeceutical Value of Herbal Extracts As Natural Ingredients
and Novel Technologies in Anti-aging.” J. Med. Plants Res., 5:
3074–3077.
[68] Barbulova, A., A. Tito, A. Carola, M. Bimonte, F. de
Laurentis, P. DʼAmbrosio, F. Apone, G. Colucci, I. Monoli, M.
Cucchiara and J. Hill. 2010. “Raspberry Stem Cell Extract to
Protect Skin from Inflammation and Oxidative Stress.” Cosmeics
and Toiletries, 125(7): 38–47.
[69] Dai, J. and R. J. Mumper. 2010. “Plant Phenolics: Extraction,
Analysis and Their Antioxidant and Anticancer Properties.”
Molecules, 15(10): 7313–7352.

[70] Nakagawa, M., K. Kawai, and K. Kawai. 1995. “Contact
Allergy to Kojic Acid in Skin Care Products.” Contact Dermatitis,
32(1): 9-13.
[71] Holloway, V. L. 2003. “Ethnic Cosmetic Products.”
Dermatologic Clinics, 21(4): 743-749.
[72] Arakane, K. 2005. “UV Care” in P. Elsner and H. I. Maibach
(eds.). Cosmeceuticals and Active Cosmetics: Drugs Versus
Cosmetics, Cosmetics Science and Technology Series. Boca Raton:
Taylor & Francis.
[73] Fitzpatrick, R. E. and E. F. Rostan. 2003. “Reversal of
Photodamage with Topical Growth Factor: A Pilot Study.” J.
Cosmet. Laser. Ther., 5(1): 25-34.
[74] Harber, L. C. and D. R. Bickers. 1989. Photosensitivity
Diseases: Principles of Diagnosis and Treatment. 2nd Edition.
Toronto: B. C. Decker.
[75] Brivika, K. and H. Sies. 1994. “Nonenzymatic Antioxidant
Defense System” in. B. Frei (ed.). Natural Antioxidants in Human
Health and Disease. New York: Academic Press.
[76] Englard, S. and S. Seifter. 1986. “The Biochemical Function
of Ascorbic Acid.” Annu. Rev. Nutr., 6(1): 365-406.
[77] Gallarate, M., M. E. Carlotti, M. Trotta, and S. Bovo. 1999.
“On The Stability of Ascorbic Acid in Emulsified Systems for
Topical and Cosmetic Use.” Int. J. Pharm., 188(2): 233-241.
[78] Akerboom, T. P. M. and H. Sies. 1981. “Assay of
Glutathione, Glutathione Disulfide and Glutathione Mixed
Disulfides in Biological Samples.” Methods in Enzymology, 77:
373-382.
[79] Kobayashi, S., M. Takehana, and C. Tohyama. 1996.
“Glutathione Isopropyl Ester Redices UVB-induced Skin Damage
in Hairless Mice.” Photochem. Photobiol., 63(1): 106-110.
[80] Halliwell, B. and J. M. C. Gutteridge. 1989. Free Radicals in
Biology and Medicine. Oxford: Clarendon Press.
[81] Ames, B. N., R. Cathcart, E. Schwiers, and P. Hochstein.
1981. “Uric Acid Provides An Antioxidant Defense in Humans
Against Antioxidant and Radical-caused Aging and Cancer: A

Hypothesis.” Proceedings of the National Academy of Sciences,
78(11): 6858-6862.
[82] Wagner, D. K., C. Collins-Lech, and P. Sohnle. 1986.
“Inhibition of Neutrophile Killing of Candida albicans
Pseudohyphae by Substances which Quench Hypochlorous Acid.”
Infect. Immunol., 51(3): 731-735.
[83] Traber, M. G. and H. Sies. 1996. “Vitamin E in Humans-
Demand and Delivery.” Annu. Rev. Nutr., 16(1): 321-347.
[84] Kamal-Eldin, A. and L. A. Appelqvist. 1996. “The Chemistry
and Antioxidant Properties of Tocopheols and Tocotrienols.”
Lipids, 31(7): 671-701.
[85] Roshchupkin, D. I., M. Y. Pistsov, and A. Y. Potapenko.
1971. “Inhibition of Ultraviolet Light-induced Erythema by
Antioxidants.” Arch. Dermatol. Res., 266(1): 91-94.
[86] Darr, D., S. Dunston, H. Faust and S. Pinnell. 1996.
“Effectiveness of Antioxidants (Vitamin C and Vitamin E) with
and without Sunscreens As Topical Photoprotectants.” Acta Derm
Vcnereol (Stockh), 76: 264-268.
[87] Jurkiewicz, B. A., D. L. Bissett, and G. R. Buettner, “Effect of
Topically Applied Tocopherolbon on Ultraviolet Radiation-
mediated Free Radical Damage in Skin.” J. Invest. Dermatol.,
104(4): 484-488.
[88] Kramer, K. A. and D. C. Liebler. 1997. “UVB Induced
Photooxidation of Vitamin E.” Chem. Res. Toxicol., 10(2): 219-
224.
[89] Lopez-Torres, M., J. J. Thiele, Y. Shindo, D. Han and L.
Packer. 1998. “Topical Application of α-tocopherol Modulates The
Antioxidant Network and Dimishes Ultraviolet-induced Oxidative
Damage in Murine Skin.” Brit. J. Dermatol., 138(2): 207-215.
[90] Thiele, J. J. and S. Ekanayake-Mudiyanselage. 2007.
“Vitamin E in Human Skin: Organ-specific Physiology and
Considerations for Its Use in Dermatology.” Molecular Aspects of
Medicine, 28(5): 646-667.
[91] Ekanayake-Mudiyanselage, S., A. Tavakkol, T. G. Polefka, Z.
Nabi, P. Elsner, and J. J. Thiele. 2005. “Vitamin E Delivery to

Human Skin by A Rinse-off Product: Penetration of α-tocopherol
Versus Wash-out Effects of Skin Surface Lipids.” Skin Pharma.
Skin Physiol., 18(1): 20-26.
[92] Carraro, C. and M. A. Pathak. 1988. “Studies on The Nature
of In Vitro and In Vivo Photosensitization Reactions by Psoralens
and Porphyrins.” J. Invest. Dermatol., 90(3): 267-275.
[93] Youssefi, A. A., I. Emerit, and J. Feingold. 1994. “Oxyradical
Involvement in PUVA-induced Skin Reactions. Protection by
Local Application of SOD.” Eur. J. Dermatol., 4(5): 389-393.
[94] Filipe, P., I. Emerit, J. Vassy, J. P. Rigaut, E. Martin, J.
Freitas, and A. Fernandes. 1997. “Epidemal Localization and
Protective Effects of Topically Applied Superoxide Dismutase.”
Exp. Dermatol., 6(3): 116-121.
[95] Podda, M., M. Ralis, M. G. Traber, L. Packer and H. I.
Maibach. 1996. “Kinetic Study of Cutaneous and Subcutaneous
Distribution Following Topical Application of [7, 8-14C]rac-a-
lipoic Acid into Hairless Mice.” Biochem. Pharmacol., 52(4): 627-
633.
[96] Fuchs, J. and R. Milbradt. 1994. “Antioxidant Inhibition of
Skin Inflammation Induced by Reactive Oxidants: Evaluation of
The Redox Couple Dihydrolipoate/lipoate.” Skin Phatmacol., 7(5):
278-284.
[97] Wang, Z. Y., R. Agarwal, D. R. Bickers, and H. Mukhtar.
1991. “Protection Against Ultraviolet B Radiation-induced
Photocarcinogenesis in Hairless Mice by Green Tea Polyphenols.”
Carcinogenesis, 12(8): 1527-1530.
[98] Katiyar, S. K., M. S. Matsui, C. A. Elmets, and H. Mukhtar.
1999. “Polyphenolic Antioxidant (-)-Epigallocatechin-3-Gallate
from Green Tea Reduces UVB-Induced Inflammatory Responses
and Infiltration of Leukocytes in Human Skin.” Photochem.
Photobiol., 69(2): 148-153.
[99] Freund, R. M. 2010. A More Beautiful You: Reverse Aging
Through Skin Care, Plastic Surgery and Lifestyle Solutions. New
York: Sterling Publishing Co. Inc.
[100] Dureja, H., D. Kaushik, M. Gupta, V. Kumar, and V. Lather.

2005. “Cosmecuticals: An Emerging Concept.” Indian J.
Pharmacol., 37(3): 155-159.
[101] W. C. Govier. 1990. “Sunscreen Composition.” U.S. Patent
4900541.
[102] Stalling, A. F. and M. P. Lupo. 2009. “Practical Uses of
Botanicals in Skin Care.” The Journal of Clinical and Aesthetic
[103] Fitzpatrick, R. E. 2005. “Use of Growth Factors in
Cosmeceuticals” in. P. Elsner and H. I. Maibach (eds.).
Francis.
[104] Naughton, G., E. Pinney, J. Mansbridge, and R. Fitzpatrick.
2001. “Tissue-Engineered Derived Growth Factors As A Topical
Treatment of Rejuvenation of Photodamaged Skin.” Journal of
Investigative Dermatology, 117(2): 543-543.
[105] Madnani, N. and K. Khan. 2013. “Hair Cosmetics.” Indian J.
Dermatol., Venereol. and Leprol., 79(5) :654-667.
[106] Grollier, J. F. and G. Rosenbaum. 1990. “A Cosmetic
Composition for The Treatment of Hair, in Particularly Oily Hair,
Based on Extract of Yarrow (Azhillea millefolium L).” U. S. Patent
4948583.
[107] Mausner, J. J. 1979. “Protein Shampoo.” U. S. Patent
4140759.
[108] Shuster, S. 1984. “The Aetiology of Dandruff and The Mode
of Action of Therapeutic Agents.” Br. J. Dermatol., 111(2): 235-
242.
[109] Faergemann, J. 1987. “Seborrheoic Dermatitis and
Pityrosporum Orbiculare: Treatment of Sebborrheic Dermatitis of
The Scalp with Miconazole-Hydrocortisone (Dactacort),
Miconazole and Hydrocortisone.” The Pediatric Infectious Disease
Journal, 6(6): 584.
[110] Faergemann, J. 1. “Treatment of Seborrhoeic Dermatitis of
The Scalp with Ketoconazole Shampoo. A Double-Blind
Study." Acta Dermato-Venereologica, 70(2): 171-172.

[111] Warner, R. R., J. R. Schwartz, Y. Boissy, and T. L. Dawson.
2001. “Dandruff Has An Altered Stratum Corneum Ultrastructure
That Is Improved with Zinc Pyrithione Shampoo.” J. Am. Acad.
Dermatol., 45(6): 897-903.
[112] Zeharia, A., M. Mimouni, and D. Fogel. 1996. “Treatment
with Bifonazole Shampoo for Scalp Seborrhea in Infants and
Young Children.” Ped. Dermatol., 13(2): 151-153.
[113] Ellis, J. A., S. Panagiotopoulus, A. Akdeniz, G. Jerums, and
S. B. Harrap. 2005. “Androgenic Correlates of Genetic Variation in
The Gene Encoding 5 Alpha-Reductase Type 1.” J. Hum. Genet.,
50(10): 534-537.
[114] Bazzano, G. S., N. Terezakis, and W. Galen. 1986. “Topical
Tretinoin for Hair Growth Promotion.” J. Am. Acad. Dermatol.,
15(4): 880-893.
[115] Weissmann, A., J. Bowden, and B. L. Frank. 1985.
“Antiandrogenic Effects of Topically Applied Spironolactone on
The Hamster Flank Organ.” Arch. Dermatol., 121(1): 57-62.
[116] Abramowicz, M. 1998. “Propecia and Rogaine Extra
Strength for Alopecia.” The Medical Letter, 40: 25-27.
[117] Sawaya, M. E. 1998. “Novel Agents for The Treatment of
Alopecia.” Seminars in Cutaneous Medicine and Surgery, 17(4):
276-283.
[118] Stamatiadis, D., M. C. Bulteau-Portois, and I. Mowszowizc.
1998. “Inhibition of 5a-reductase Activity in Human Skin by Zinc
and Azelaic Acid.” Br. J. Dermatol., 119(5): 627-632.
[119] Zhou, Z., R. Lenk, A. Dellinger, D. MacFarland, K. Kumar,
S. R. Wilson, and C. L. Kepley. 2009. “Fullerene Nanomaterials
Potentiate Hair Growth.” Nanomedicine: Nanotechnology, Biology
and Medicine, 5(2): 202–207.
[120] Breakspear, S., M. Fukuhara, T. Itou, Y. Hirano, M. Nojiri,
A. Kiyomine, and S. Inoue. 2012. “Alignment Control and
Softness Creation in Hair with Glycylglycine.” Journal of
Cosmetic Science, 64(1): 19-33.
[121] Nazir, H., P. Lv, L. Wang, G. Lian, S. Zhu, and G. Ma. 2011.
“Uniformsized Silicone Oil Microemulsions: Preparation,

Investigation of Stability and Deposition on Hair Surface.” Journal
of Colloid and Interface Science, 364(1): 56-64.
[122] Hu, Z., M. Liao, Y. Chen, Y. Cai, L. Meng, Y. Liu, N. Lv, Z.
Liu,and W. Yuan. 2012. “A Novel Preparation Method for Silicone
Oil Nanoemulsions and Its Application for Coating Hair with
Silicone.” Int. J. of Nanomedicine, 7: 5719-5724.
[123] Sinclair, R. D. 2007. “Health Hair: What Is It?.” Journal of
Investigative Dermatology Symposium Proceedings, 12(2): 2-5.
[124] Gode, V., N. Bhalla, V. Shirhatti, S. Mhaskar, Y. Kamath.
2012. “Quantitative Measurement of The Penetration of Coconut
Oil into Human Hair Using Radiolabeled Coconut Oil.” J. Cosmet.
Sci., 63(1): 27-31.
[125] Dias, M. F R. G. 2015. “Hair Cosmetics: An Overview.” Int.
J. Trichol., 7(1): 2-15.
[126] Starley, I. F., P. Mohammed, G. Schneider, and S. W.
Bickler. 1999. “The Treatment of Paediatric Burns Using Topical
Papaya.” Burn, 25(7): 636-639.
[127] Eshun, K. and Q. He. 2004. “Aloe Vera: A Valuable
Ingredient for The Food, Pharmaceutical and Cosmetic Industries-
A Review.” Critical Reviews in Food Science and Nutrition, 44(2):
91-96.
[128] Chithra, P., G. B. Sajithlal, and G. Chandrakasan. 1998.
“Influence of Aloe Vera on The Glycosaminoglycans in The
Matrix of Healing Dermal Wounds in Rats.” J. Ethnopharmacol.,
59(3): 179-186.
[129] Neudecker, B. A., H. I. Maibach, and R. Stern. 2005.
“Hyaluronan: The Natural Skin Moisturizer” in. P. Elsner and H. I.
[130] Smeets, J. W. H., R. M. D. Pater, and J. W. J. Lambers.
1997. “Enzymatic Synthesis of Ceramides and Hybrid Ceramides.”
U. S. Patent 005610040A.
[131] Cho, S. H., L. J. Frew, P. Chandar, and S. A. Madison. 1995.
“Synthetic Ceramides and Their Use in Cosmetic Compostions.”

U. S. 005476671A.
[132] Singh, A., P. K. Sharma, and G. Garg. 2010. “Natural
Products As Preservatives.” Int. Journal of Pharma. and
Bioscience, 1(4): 601-612.
[133] Gould, G. W. 1996. “Industry Perspective on The Use of
Natural Antimicrobials and Inhibitors for Food Applications.” J.
Food Protection, 59(suppl.): 82-86.
[134] Naqvi, S. A. H., M. S. Y. Khan, and S. B. Vohora. 1990.
“Antibacterial, Antifungal and Anthelmintic Investigations on
Indian Medicinal Plants.” Fitoterapia, 61(2): 169-171.
[135] Bele, A. A., V. M. Jadhav, S. R. Nikam, and V. J. Kadam.
2009. “Antibacterial Potential of Herbal Formulation.” Res. J.
Microbiol., 4(4) 164-167.
[136] Elder, R. L. 1984. “Final Report on The Safety Assessment
of Methylparaben, Ethylparaben, Propylparaben and
Butylparaben.” Journal of the American College of Toxicology,
3(5): 147–209.
[137] Soni, M. G., S. L. Taylor, N. A. Greenberg, and G. A
Burdock. 2002. “Evaluation of The Health Aspects of
Methylparaben: A Review of The Published Literature.” Food and
Chemical Toxicology, 40(10): 1335-1373.
[138] Ramlogan, D., D. A. Basketter, and M. H. Beck. 2004.
“Methyldibromoglutaronitrile: An Increasing Important Allergen in
UK.” Exogenous Dermatology, 2(4): 184-189.
[139] Lupo, M. P. 2001. “Antioxidants and Vitamins in
Cosmetics.” Clin. Dermatol., 19(4): 467-473.
[140] Ingolfsdottir, K. 2002. “Usnic acid”. Phytochemistry, 61(7):
729-736.
[141] Bakkali, F., S. Averbeck, D. Averbeck, and M. Idaomar.
2008. “Biological Effects of Essential Oils - A Review.” Food
Chem. Toxicol., 46(2): 446-475.
[142] Pinto, E., C. Pina-Vaz, L. Salgueiro, M. J. Gonçalves, S.
Costa-de-Oliveira, C. Cavaleiro, A. Palmeira, A. Rodrigues, J.
Martinez-de-Oliveira. 2006. “Antifungal Activity of The Essential
Oil of Thymus pulegioides on Candida, Aspergillus and

Dermatophyte Species.” J. Med. Microbiol., 55(33):1367-1373.
[143] Tian, J., X. Ban, H. Zeng, J. He, Y. Chen, Y. Wang. 2012.
“The Mechanism of Antifungal Action of Essential Oil from Dill
(Anethum graveolens L.) on Aspergillus Flavum.” PLoS One, 7(1):
e30147.
[144] Shao, X., S. Cheng, H. Wang, D. Yu, and C. Mungai. 2013.
“The Possible Mechanism of Antifungal Action of Tea Tree Oil on
Botrytis cinerea.” J. Appl. Microbiol., 114(6): 1642–1649.
[145] Antignac, E., G. J. Nohynek, T. Re, J. Clouzeau, H. Toutain.
2011. “Safety of Botanical Ingredients in Personal Care
Products/Cosmetics.” Food Chem. Toxicol. 49(2): 324-341.
[146] Botto, J., K. Cucumel, C. Dal Farra, and N. Domloge,
“Treatment of Human Cells with HSP70-riched Yeast Extract
Enhances Cell Thermotolerance and Resistance to Stress,” Journal
of Investigative Dermatology, 117(2): 452.
[147] Brown, A. D. 1976. “Microbial Water Stress.” Bacteriol.
Rev., 40(4): 803-846.
[148] Lippert, K. and E. A. Galinski. 1992. “Enzyme Stabilization
by Ectoine-Type Compatible Solutes: Protection Against Heating,
Freezing and Drying.” Appl. Microbiol. Biotechnol., 37(1): 61-65.
[149] Sauer, T. and E. A. Galinski. 1998. “Bacterial Milking: A
Novel Bioprocess for Production of Compatible Solutes.”
Biotechnol. Bioeng., 57(3): 306-313.
[150] Buommino, E., C. Schiraldi, A. Baroni, I. Paoletti, M.
Lamberti, M. De Rosa, and M. A. Tufano. 2005. “Ectoine from
Halophilic Microorganisms Induces The Expression of hsp70 and
hsp70B in Human Keratinocytes Modulating The Proinflammatory
Response.” Cells Stress & Chaperones, 10(3): 197-203.
[151] Motitschke, L., H. Driller, and E. A. Galinski. 2000. “Ectoin
and Ectoin Derivatives As Moisturixer in Cosmetics.” U. S.
US6060071.
[152] Draize, J. H., G. Woodward, and H. O. Calvery. 1944.
“Methods for The Study of Irritation and Toxicity of Substances
Applied Topically To The Skin and Mucous Membranes.” Journal
of Pharmacology and Experimental Therapeutics, 82(3): 377-390.

[153] Poumay, Y. and A. Couquette. 2007. “Modeling The Human
Epidermis In Vitro, Tools for Basic and Applied Research.” Arch.
Dermatol. Res., 298(8): 361-369.
[154] Triglia, D., S. Sherard-Braa, T. Donnelly, I. Kidd, and G. K.
Naughton. 1991. “A Three-Dimensional Human Dermal Substrate
for In Vitro Toxicological Studies.” in A. M. Goldberg (ed.).
Alternative Methods in Toxicology. New York: Mary Ann Liebert.
[155] Celik, F. and S. Ercisli. 2009. “Lipid and Fatty Acid
Composition of Wild and Cultivated Red Raspberry Fruits (Rubus
idaeus L.).” J. Med. Plants Res., 3(8): 583–585.
[156] Apone, F., A. Tito, A. Carola, S. Arciello, A. Tortora, L.
Filippini, I. Monoli, M. Cucchiara, S. Gibertoni, M. J. Chrispeels
and G. Colucci. 2010. “A Mixture of Peptides and Sugars Derived
from Plant Cell Walls Increases Plant Defense Responses to Stress
and Attenuates Ageing-associated Molecular Changes in Cultured
Skin Cells.” Journal of Biotechnology, 145(4): 367–376.
[157] Nacht, S. 1995. “Encapsulation and Other Topical Delivery
Systems.” Cosmet. Toiletries, 110(9): 25-30.
[158] Klein, K. 2005. “Formulating Cosmetic Emulsions: A
Beginner’s Guide.” Cosmet. Toiletries, 120(1): 75-78.
[159] Bangham, A. D., M. M. Standish, and J. C. Watkins. 1965.
“Diffusion of Univalent Ions Across The Lamellae of Swollen
Phospholipids.” J. Mol. Biol., 13(1): 238.
[160] Muller, R. H., S. Benita, and B. Bohms. 1998. Emulsions
and Nanosuspensions for The Formulation of Poorly Soluble
Drugs. Boca Raton: CRC Press.
[161] Muller, R. H., M. Radtke, and S. A. Wissing. 2000. “Solid
Lipid Nanoparticles (SLN) and Nanostructured Lipid Carriers
(NLC) in Cosmetic and Dermatological Preparations.” Advanced
Drug Delivery Reviews, 54: S131-S155.
[162] Florence, A. T. and D. Whitehill. 1981. “Some Features of
Breakdown in Water-in-Oil-in-Water Multiple Emulsions.” J.
Colloid. Interface Sci., 79(1): 243-256.
[163] Kreilgaard, M. 2002. “Influence of Micremulsions on
Cutaneous Drug Delivery.” Advanced Drug Delivery Reviews, 54:

77-98.
[164] Magdassi, S. 1997. “Delivery Systems in Cosmetics.”
Colloids Surfaces A: Physicochemical and. Engineering Aspects,
123: 671-679.
[165] United States. Congress. House. Committee on Small
Business. Subcommittee on Regulation and Business
Opportunities. (1989). Potential Health Hazards of Cosmetic
Products: Hearings before The Subcommittee on Regulation and
Business Opportunities of the Committee on Small Business, House
of Representatives, One Hundredth Congress, Second Session,
Washington: July 14 and September 15.
[166] Kligman, A. M. 2005. “Cosmeceuticals: A Broad Spectrum
Category between Cosmetics and Drugs” in P. Elsner and H. I.
[167] Dreger, M. and K. Wielgus. 2013. “Application of Essential
Oils As Natural Cosmetics Preservatives - A Review.” Herba
Polonica, 59(4): 142-156.
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Cosmeceuticals and Natural Cosmetics

Chapter · December 2017

Haiza Muda Azila Aziz

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It is human nature to desire beauty. As such, the use of cosmetics

There are three major trading blocks for cosmetics namely

6.2 SKIN COSMECEUTICALS

Skin is a physical barrier that protects the internal environment

Moisturizers that increase hydration and make stratum corneum

Retinoids are one of the most common and popular cosmeceuticals

sulfone and adapalene. Retinoids have adverse effects associated

6.2.3 Hydroxy Acids

Hydroxy acids are also very popular as cosmeceuticals ingredients.

The current trend in cosmetics embraces the back to nature

resistance, to degrade histamine, to protect against free-radical

ginger [45]. Hydroxyacids used for epidermal shedding, hydration

6.2.5 Amino Acids and Derivatives

Amino acids are molecules with an amino group and a carboxylic

serine and vitamin B6 has also been developed for a functional

6.2.6 Depigmentation Agents

Facial pigmentary disorders can be acquired (melasma, sun

ingredient in Japan, EU and Australia in 2001 and a proposed ban

6.3 SKIN COSMECEUTICALS: SUN CARE

The pathology of photoaged skin has been associated with a

6.3.1 Antioxidant Defense Systems

To counteract the harmful effects of ROS the skin is equipped with

transport of topically applied vitamin C needs sophisticated

increase levels of vitamin E in stratum corneum of human skin and

Regular use of an effective sunscreen is important in protecting the

UV radiations resulting in invisible sunblock. A sunscreen

6.3.3 Growth Factors

Vitamin C and vitamin E are common ingredients in

solution containing a mixture of amino acids, vitamins,

6.4 HAIR COSMECEUTICALS

weight of polyphenolic derivatives [106]. A hair care formulation

be obtained from wheat, rye and barley. It can act as an antiadrogen

6.5 NATURAL COSMETICS

As stated before, cosmeceuticals can be natural or synthetic. A

The natural body care segment includes nine categories:

6.5.1 Active Ingredients

The following is a list of some of the natural active ingredients

6.5.1.2 Aloe Vera

The aloe plant, being a cactus plant, contains over 75 different

6.5.1.3 Hyaluronic Acid

Hyaluronan or hyaluronic acid (HA) is a glycosaminoglycan

Ceramide is a key intermediate in the biosynthesis of all complex

6.5.2 Formulation Challenges of Natural Cosmetics

The presence of preservatives in cosmetic products is

Parabens are widely used as cosmetic preservatives in a large

have a use in over 13, 200 formulations [136]. Paraben

This is an inexpensive and effective preservative that is widely

Quaternium-15 is a preservative found in many cosmetics. It is a

6.5.2.4 Euxyl K 400

The newest preservative system found in cosmetics, Euxyl K 400,

(1) 1, 2- dibromo-2, 4-dicyanobutane