Academic Sciences International Journal of Current Pharmaceutical Research

ISSN- 0975-7066 Vol 6, Issue 3, 2014

Review Article
LIPOSOMES AS CARRIERS IN SKIN AGEING

VARSHNEYA APARAJITA*, PADMINI RAVIKUMAR

Dr. Bhanuben Nanavati College of Pharmacy, Gate No.1, Mithibai College Campus, V.M. Road,Vile Parle (West), Mumbai 400056
Email: [email protected]
Received: 04 June 2014, Revised and Accepted: 16 June 2014
ABSTRACT
Ageing is an inevitable phenomenon. Similar to other organs, skin is also subject to an intrinsic ageing process. Additionally, skin ageing is also
influenced by various environmental factors. Existing conventional formulations have limited efficacy because skin serves as a rate limiting barrier
for percutaneous absorption of drugs. This has led to the evolution of various novel drug delivery systems. Among these liposomes have received
considerable attention due to the numerous advantages they offer. Liposomes, submicroscopic spherical vesicles, were discovered in 1960’s. Since
then, they have gained popularity as potential carriers for drugs, diagnostics, nutrients, vaccines and other bioactive agents. Liposomes find
applications in pharmaceutical, cosmetics and other industrial fields. Various topical actives that have been found to be efficacious in delaying the
signs of ageing have been formulated as liposomes resulting in enhanced delivery, biocompatibility, and reduced toxicity. This review focusses on
therapeutic use of liposomes in skin ageing.
Keywords: Liposome, Ageing, Topical application, Antioxidants.

INTRODUCTION environmental factors, solar ultraviolet (UV) radiation is a

prominent causative factor for skin ageing, termed as photoageing.
As the global population's median age is increasing, ageing is a major From studies it is now clear that both UVB (290–320 nm) and UVA
concern among people worldwide. Consumers’ desire to maintain (320–400 nm) radiations contribute to photoageing. UVB acts
appealing look has led to the emergence of ever-expanding cosmetic preferentially on the epidermis where it damages DNA in
market. Anti-ageing products are flourishing as a lot of emphasis is keratinocytes and melanocytes and causes production of proteolytic
laid on youthful appearance[1]. Ageing is unpreventable and thus it enzymes which affect the dermis. UVA radiation penetrates far more
has aroused the interest of researchers across the globe to curb it to deeply on average and hence exerts direct effects on both the
some extent. Various advanced technologies such as facelifts, laser, epidermal and the dermal compartments[8].
botox, microdermabrasion etc. have gained an impetus in recent
years but are less preferred by the local masses due to the Oxidative stress, an imbalance between the production of reactive
associated drawbacks, high cost and invasive nature. Topical oxygen species (ROS) and antioxidant defenses leads to cellular and
application of anti-ageing formulations has been adopted as an tissue damage[9]. According to the free radical theory of ageing,
important strategy as they serve as a non-invasive alternative to reactive oxygen species, primarily arising from oxidative cell
slow the effects of ageing on the skin. The main hurdle in topical metabolism, play a major role in both chronological and
administration of actives is the barrier nature of the skin. The photoageing. Several anti-oxidative mechanisms operate in body to
stratum corneum or horny layer has been identified as the principal combat the harmful effect of free radicals.
barrier for penetration of most drugs[2]. The delivery of actives
from conventional formulations is generally compromised. Thus These mechanisms deteriorate with increasing age causing damage
there arises the need for a suitable carrier to increase drug to cellular components leading to cellular ageing. The superoxide
deposition. A plethora of microparticulate carrier systems have radicals and H 2 O 2 formed by the mitochondria in the course of
evolved which improve drug delivery to skin. Recently, Liposome normal metabolism, causes damage to nucleic acid, lipids and
based formulations have been found to be extremely promising for proteins including collagen. This cumulative collagen damage,
topical delivery[3],[4]. disrupts the structural integrity of skin and contributes to wrinkle
formation[10].
Intrinsic and extrinsic factors of ageing
Anti-ageing remedies
A comprehensive grading scale for skin ageing has been validated,
which categorizes skin ageing as: laxity (sagging), rhytids (wrinkles) There are several facial treatments available that promise to cure
and photoageing which is further sub-classified as erythema the above mentioned problems. These include facelifts, botox,
(redness), dyspigmentation (brown discolorations), solar elastosis derma-abrasion, facial peels, growth hormones, collagen injections
(yellowing), keratoses (abnormal growths) and poor texture[5]. etc. These techniques have their own pros and cons. Mainly due to
Ageing is due to both genetic and environmental factors popularly their invasive nature, risk of adverse effects and cost, these
termed as intrinsic (chronological) and extrinsic factors of ageing. procedures have not reached the common folks. Thus the focus has
Various theories have attributed intrinsic skin ageing to factors such shifted to topical anti-ageing products. Over the counter (OTC) anti-
as oxidative stress, genetic mutations and decrease of several ageing products are a billion-dollar industry to which even young
hormone levels. The deficiency in oestrogens and androgens cause patients who wish to prevent the ageing process contribute[11].
dryness, wrinkling, epidermal atrophy, collagen breakdown and loss
of elasticity[6]. Collagen, a natural protein present in dermis, The common ingredients in anti-ageing products include
imparts elasticity to the skin. With advancing age, the production of antioxidants, moisturisers, sunscreen agents, topical peptides,
collagen decreases leading to loss in elasticity and production of hydroxy acids and retinoids. As the root cause of skin ageing is
wrinkles. When young, epidermis of the skin stretches and holds oxidative stress, the use of antioxidants has attained priority.
large amount of moisture due to the presence of fibers called elastin Naturally occurring antioxidants such as Vitamin A, C, E, squalene,
and also a layer of fat in the subcutaneous level of skin. Elastase is coenzyme Q-10 donate electron and neutralize free radicals. Thus
the only enzyme that is capable of breaking down elastin (an various OTC products claiming to be anti-ageing products are rich in
insoluble elastic fibrous protein). Elastin together with collagen is such antioxidants. Antioxidants are promising in photoprotection
responsible for the mechanical properties of connective tissue[7]. All with negligible side effects at physiological concentrations[12]. For
this is lost with advancing age leading to sagging appearance of effective photoprotection, it is necessary that desirable amount of
epidermal layer of skin. Among all extrinsic factors i.e. antioxidant reaches the site of action. However, delivery of drugs
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through conventional topical preparations like gels and creams is organized structures, consisting of concentric bilayered vesicles in
compromised due to barrier properties of the skin. Skin has been which an aqueous volume is entirely enclosed by a membraneous
described as a waterproof barrier which does not allow hydrophilic lipid bilayer[15].Therefore both hydrophobic (in the bilayers) and
substances or high molecular weight substances to pass through it. hydrophilic substances (in the aqueous compartment) can be
Thus the formulation of dermatologic cosmetics is difficult when entrapped in liposomes. Liposomes thus protect the entrapped
high concentration of such actives is required in cutis. The skin’s molecule from degradation. Moreover they offer sustained and
brick and mortar structure hinders drug deposition. Moreover targeted release[16]. The main objective of using liposomes as drug
vitamins have poor stability and lose their potency on exposure to carriers is to achieve selective and sufficiently high localization of
UV light. Thus selection of proper carrier is of paramount active drug at disease sites. In this respect, the liposomes differ from
importance so that there is increase in drug deposition and drug is other controlled release systems, in which drug release occurs either
protected from photodegradation[13]. Various novel drug delivery in plasma or at the site of administration. Owing to their biological
systems have been explored to overcome above mentioned origin they are nontoxic in nature and are easily re-absorbed from
problems. Of which colloidal carriers called Liposomes have the epidermis into the deepest layers. The encapsulation of drugs
received considerable attention. into liposomes, for topical use, gives a higher drug concentration at
the intended site of action, thereby enhancing the localized effects
Liposomes but at the same time minimizing unwanted systemic side effects[17].
Liposomes were first described by British haematologist Dr. Alec D Thus the topical application of liposomes offer a wide range of
Bangham FRS in 1961(published 1964), at the Babraham Institute, advantages including increased moisturization, restoring action,
biodegradability, biocompatibility and extended and slow dermal
in Cambridge. They were discovered when Bangham and R. W.
release[18].
Horne were testing the institute's new electron microscope by
adding negative stain to dry phospholipids. They observed clear Liposomes have been widely used as drug carriers for their
resemblance of the lipid structures to the plasmalemma and the innumerable utilitarian aspects. But their major limitation is
microscope pictures served as the first real evidence for the cell instability[19]. The vesicles are prone to fusion, aggregation, poor
membrane being a bilayer lipid structure[14]. retention and drug leakage with time. According to recent research,
liposomes break into pieces the moment they hit the skin’s surface,
or very soon after that. Liposomes cannot be transported into
deeper layers. Experiments using amphiphilic and hydrophilic
fluorescently labeled molecules show that the diffusion of liposomes
in stratum corneum is very heterogeneous on a microscopic scale
and that the penetration of intact liposomes is highly compromised
by the skin barrier[20].
Composition of Liposomes
Liposome composition includes natural and/or synthetic
phospholipids. Phosphatidylcholine (lecithin) and
phosphatidylethanolamine constitute the two major structural
components of most biological membranes. Liposome bilayers may
also contain other constituents such as cholesterol or surfactants.
Cholesterol has been largely used to improve the bilayer
characteristics of the liposomes. It improves the membrane fluidity,
Fig.1: Structure of Liposome
bilayer stability and reduces the permeability of water soluble
molecules through the membrane. A clear advantage of liposomes is
The term liposome was coined from two Greek words: 'Lipos' the fact that the lipid membrane is made from physiological lipids
meaning fat and 'Soma' meaning body. Liposomes are highly which decreases the danger of acute and chronic toxicity[21].

Fig. 2: Methods of liposome preparation [14]

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Mechanism of action of liposomes The function of moisturizers is to keep the stratum corneum
hydrated. Occlusive compounds promote the penetration of active
The activity of liposomal formulations in ageing is attributed to its
compounds owing to better skin hydration[18]. As liposomes are
occlusive action, enhanced bioavailability, protection of active
composed of lipids, even empty liposomes have found to be useful in
ingredients, reduction of systemic absorption and reduction of side
skin hydration. They simply contribute lipids to the stratum
effects. The exact mechanism by which the liposomes work is highly
debated but the occlusive effect of topical liposomes is already corneum and cosmetics containing liposomes rely on this effect[22].
proven. Dehydrated skin loses elasticity and becomes rough and Liposome as a carrier itself offers advantages because lipids are well
flaky. Moisturizing products constitute one of the largest and most hydrated and can reduce the dryness of the skin which is a primary
important skin care product category. cause for skin ageing[23].

Table 1: Commonly used ingredients in anti-ageing formulations[31]

Ingredient Action Source
Allantoin Skin Soothing, moisturizing Comfrey

Aloe vera Softens skin, moisturizing Aloe barbadensis

Ascorbic acid Antioxidant, photoprotectant Vitamin C (citrus fruits)
Arnica Astringent and soothing Arnica montane
Arjunolic extract Antioxidant and anti-inflammatory Terminalia arjuna

Beta‐Carotene Minimizes lipid peroxidation and Carrots and tomatoes

cellular antioxidant

Boswellia Anti-inflammatory and anti-ageing Boswellia serrata

Calendula Soothes, softens skin, promotes cell formation. Calendula officinalis

Centella Skin conditioning agent, increases collagen Centella asciatica

production, improves texture and integrity of skin,
and reduces appearance of stretch marks

Coriander seed oil Anti-inflammatory and anti-irritant, skin‐ lightening Coriandrum sativa
properties

CoenzymeQ10(Ubiquinone) Cellular antioxidant Naturally occurring in skin

Cucumber Refreshes and tightens pores Cucumis sativus
Essential fatty acids Smoothens, moisturizes and Linolenic and arachidonic acid
protects

Furfuryladenine Improves hydration and texture of Plant growth hormone

skin

Lupeol Antioxidant and skin conditioning Cratacva nurvula

agent

Ginkgo Antioxidant that smoothes, Ginkgo biloba

rejuvenates and promotes youthful appearance
Green tea extract Antioxidant Green teas (Camellia sinensis)
Kinetin Antioxidant Plants and yeast
Licorice extract Skin whitening properties, Glycyrrhiza glabra
Oleanolic extract Antioxidant, improves Olive leaf
texture and integrity of skin

Panthenol Builds moisture and soothes Provitamin B5 (broccoli, calf's liver, turnip
irritation greens)

Pycnogenol Antiageing effect, protects collagen Grape seed extract

Retinoic acid Promotes cell renewal and improves circulation to Vitamin A(green leafy vegetables)
skin

Sodium hyaluronate Lubricant between skin tissues and maintains natural Natural protein
moisture

Rosemary extract Antioxidant, antimicrobial, and Rosemarinus officinalis

anti‐inflammatory

Tetrahydrocurcuminoides, turmeric oil Antioxidant and antiageing Curcuma longa

Tocopherol Antioxidant, improves hydration and cellular Vitamin E (vegetable oils)
regeneration of skin
Ursolic acid Anti-inflammatory, collagen buildup Rosemarinus officinalis

Witch hazel Tightens pores, tones Hamamelis virginiana

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Vegetable phospholipids like soya lecithin are widely used for decrease in SOD activity was observed 24 and 48 hours after
topical applications in cosmetics and dermatology, since they have a ultraviolet irradiation. The SOD levels returned to the normal level
high content of esterified essential fatty acids, especially linoleic acid by 72 hour time period. Decreased SOD activity after ultraviolet
which is believed to increase the barrier function of the skin and exposure was lessened by pretreatment of skin with liposomal SOD.
decrease water loss within a short period of time after application. The authors suggested that this protective effect of the encapsulated
Soya phospholipids or other vegetable phospholipids, due to their SOD may have potential clinical application for photodermatologic
surface activity and their ability to form liposomes, are an ideal reactions[24].
source for possible transport of linoleic acid into the skin[24].
Sodium ascorbyl phosphate (a stable Vitamin C derivative) is an
The reports of enhanced drug delivery by liposomes have been effective radical scavenger and has the greatest potential for slowing
attributed to the lipid film produced on the skin, which increases down the detrimental effects resulting from photodamage. It is
hydration[25]. Topical liposomes reduce skin roughness because of cleaved by enzymes in the skin to release ascorbic acid. At
their interaction with the corneocytes and intercellular lipids physiological pH ascorbic acid is present mainly as the ascorbate
resulting in skin softening and smoothening[26]. anion which penetrates poorly into the skin. Thus by encapsulating
into liposomes, the penetration through the stratum corneum into
Liposomes enable better delivery of active ingredients into the the deeper layers of the skin can be improved. Foco et al. performed
deeper layers of the skin by merging with the cell membrane thus in-vitro diffusion studies of sodium ascorbyl phosphate and ex-vivo
leading to enhanced bioavailability. It is supposed that upon contact penetration experiments on pig ear epidermis membrane in a Franz
with skin, molecular mixing of liposome bilayer with intracellular diffusion cell. They observed that sodium ascorbyl phosphate
lipids in stratum corneum occurs which changes the hydration and penetrated through epidermis membrane significantly better from
thereby the structure of lipid lamellae. It is followed by enhanced liposome dispersions than from water solution[33].
permeation of lipophilic drugs into the stratum corneum and
diffusion of hydrophilic drugs into the interlamellar spaces. On the Padamwar & Pokharkar demonstrated a factorial design approach
other hand, it is also possible that some liposomes, which are for preparation of stable Vitamin E acetate liposomal formulation.
deformable enough, pass the stratum corneum intact and They presented that variables such as amount of phospholipid,
disintegrate deeper in skin layer. However there is no direct stabilizer and lipid: drug ratio have a profound effect on the vesicle
evidence confirming these mechanisms[27]. size and drug deposition in the rat skin. Gels containing liposomal
dispersion were prepared and were found to be stable for 3 months.
By virtue of encapsulating both hydrophilic and hydrophobic drugs, They also proved that liposomal formulation promotes drug
liposomes also protect the drug from degradation. Lee et al. deposition in rat skin as compared to control drug dispersion,
investigated the effect of freeze drying on liposomes. The freeze control gel and marketed cream[4].
dried ascorbyl palmitate liposomes were prepared which protected
the drug from moisture attack and could be used instantly by mixing Fang et al. examined the effect of liposomal composition on the
with water for anti-ageing and skin whitening therapy. The efficiency of transdermal catechin delivery. Catechins which possess
measurement of the time for reconstitution showed that freeze- significant antioxidant activity were encapsulated in liposomes
dried liposomes could be changed to their initial state rapidly and using anionic surfactants and ethanol. They concluded that
short term stability test under accelerated conditions confirmed that incorporation of anionic surfactants such as deoxycholic acid and
the stability of ascorbyl palmitate was considerably enhanced as dicetyl phosphate in the liposomes in presence of 15% ethanol
compared to freshly prepared liposomes. Freeze dried liposomes increased the catechin permeation by five to seven-fold as compared
also reproduced similar skin permeation and localization to the control. Skin permeation studies were conducted on mouse
properties[28]. skin. The flexibility of bilayers was suggested as an important factor
governing the enhancing effect of liposomes[34].
Since the liposomal formulations provide sustained and enhanced drug
levels in the strata, with increased localization, the incidence of Various anti-inflammatory agents have been useful topically as anti-
undesirable side-effects arising from systemic administration is ageing remedies. Manconia et al. formulated C-Phycocyanin
reduced[29]. A study conducted by Sinico et al. showed that liposomal liposomes and proved that the protein was mainly localised in the
encapsulation of trans-retinoic acid (tretinoin) helps in surmounting its stratum corneum, while there was no permeation through the whole
side effects of skin irritation (erythema, peeling and burning) and high skin. Two percent C-Phycocyanin liposomes showed drug
instability in the presence of air, light and heat[30]. accumulation higher than that of the corresponding free 2% C-
Phycocyanin gel. Liposomal encapsulation also improved its anti-
Liposomal formulations in ageing inflammatory activity[35].
Anti-ageing formulations work mainly by reducing fine lines, visible A study conducted by Yarosh et al. demonstrated that ursolic acid
wrinkles, pigmentation changes, blemishes and other incorporated into liposomes increases both the ceramide content of
environmentally related conditions of the skin. cultured normal human epidermal keratinocytes and the collagen
Antioxidants content of cultured normal human dermal fibroblasts. In clinical
tests, the ceramide content in human skin was increased over an 11-
The term “antioxidant liposome” is relatively new and refers to day period. Liposomes had effect on keratinocyte differentiation and
liposomes containing lipid soluble, water-soluble, enzymatic or dermal fibroblast collagen synthesis similar to retinoids[36].
combinations of these various antioxidants. The lipid-soluble
antioxidants that can be incorporated into liposomes include Takahashi et al. prepared liposomes encapsulating aloe gel extract
vitamin E, ubiquinones, retinoids, carotenoids (e.g., lutein, beta- by Bangham method and examined for the effects on proliferation
carotene, lycopene, astaxanthin, zeaxanthin and peridinin), lipid- and type I collagen synthesis in normal human neonatal skin
soluble flavonoids (e.g., quercetin, hesperedin, naringenin), soy fibroblasts. Liposomal aloe gel extract clearly showed higher
isoflavones (genistein and daidzein). The water-soluble antioxidants proliferation rate than that of aloe gel extract alone. In addition,
that can be used in antioxidant liposomes include ascorbate (vitamin compared to control, liposomes significantly increased the collagen
C), urate, glutathione, N-acetylcysteine, lipoic acid (or dihydrolipoic synthesis by 23%, while aloe extract alone showed a small effect.
acid, which is its reduced form), pro-cysteine, and water-soluble Liposomal aloe gel extract was also assayed for the effect on
proliferation in normal human epidermal keratinocytes. They
flavonoids (e.g. pycnogenol)[32].
observed that liposomal fractions containing 4 and 20
Topical application of enzymatic antioxidants has been postulated in microgram/mL of the extract considerably increased the
treating oxidative stress. Superoxide dismutase, catalase, proliferation rate by 77% and 101%, respectively. In comparison,
glutathione peroxidase are few endogeneous enzymatic antioxidants aloe gel extract fractions containing 4 and 20 microgram/mL of the
that serve as antioxidant defense system. The effect of a single extract increased the rate by 41% and 60%, respectively.
exposure to ultraviolet radiation on skin superoxide dismutase Accordingly, the bioavailability and skin care properties of aloe gel
(SOD) activity was examined in mice by Miyachi et al. A significant extract was significantly enhanced by liposome encapsulation[37].

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Resveratrol, a powerful natural antioxidant, was encapsulated in One such novel hypopigmenting agent is 4-n-Butylresorcinol; it has
liposomes-in-alginate microbeads by using proliposome method. an inhibitory effect against tyrosinase and tyrosinase-related
Diffusion studies showed prolonged release up to 5 hours[38]. In a protein-1. Liposome encapsulation helps in improving stabilization
similar study, Caddeo et al. investigated the possibility of improving and enhancing penetration of the product. Huh et al. conducted a
the efficacy of resveratrol, on cell proliferation and photoprotection randomized double blind vehicle-controlled and split-face
by liposomal incorporation. Oligolamellar vesicles of different lipid comparison study on 23 patients with clinical diagnosis of melasma
compositions, loaded with resveratrol, were prepared and for 8 weeks. They observed that the melanin index of the 4-n-
characterized. The effect of free and liposomal resveratrol on the butylresorcinol-treated side showed a significant decrease when
viability of HEK 293 cells and their photoprotection after UV-B compared with the vehicle-treated side. They concluded that
irradiation was assessed. Photomicrographs of the treated cells from liposome-encapsulated 4-n-butylresorcinol 0.1% cream was well
inverted light and fluorescence microscopy demonstrated tolerated and showed significant higher efficacy than vehicle alone
resveratrol effectiveness at 10µM, as well as its toxicity at higher for the treatment of melasma[47].
concentrations, based on changes in cell shape, detachment and
apoptotic features. However, liposomes prevented the cytotoxicity In a study carried out by Shigeta et al. linoleic acid was formulated
of resveratrol at high concentrations, even at 100µM, and increased as liposomal hydrogel. Liposomal linoleic acid (0.1%) showed a
the ability of resveratrol to stimulate the proliferation of the cells whitening effect comparable to 10.0% non-liposomal linoleic acid
and their ability to survive under stress conditions caused by UV-B and was far more effective than 3.0% non-liposomal linoleic acid.
light[39]. These results indicate that liposomal formulations are favorable for
the transdermal application of linoleic acid[48].
Retinoids have extensive application in cosmetics. Topical retinoid
products are one of the most important drug class to reverse Similarly, Wen et al. formulated arbutin liposomes for enhancing
cutaneous ageing with clinical efficacy proven in a number of trials skin whitening activity. It was reported that although the
that included histologic evaluation. Vitamin A is the most common permeation rate of arbutin in the liposome formulations decreased
naturally occurring retinoid, and acts by stabilizing the oxygen compared with arbutin solution, the deposition amount of arbutin in
radicals that are created after skin exposure to ultraviolet light[40]. the epidermis/dermis layers increased in liposomal formulation.
However, their therapeutic use is limited due to its toxicity, poor These results suggest that liposomal formulation could enhance the
chemical stability, and hydrophobic nature[41]. skin deposition of hydrophilic skin-whitening agents, thereby
enhancing their activities[49].
Thus antioxidant liposomes hold great potential in the treatment of
many conditions in which oxidative stress plays a prominent role. Sunscreens
Several studies have clearly indicated that the liposomal antioxidant As solar radiations are detrimental for skin, use of sunscreen is
formulations compared to that of the free non-encapsulated highly recommended to prevent the signs of ageing. Jaafari et al.
antioxidants exert a far superior protective effect against oxidative determined the influence of vehicles on the penetration of octyl
stress-induced tissue injuries. methoxycinnamate (OMC) in the stratum corneum by tape stripping
Hydroxy acids method. The experimental formulations consisted of a conventional
o/w emulsion and multilamellar (MLV) and small unilamellar (SUV)
Alpha hydroxy acids (AHAs) derived from natural sources such as liposomes. Various formulations were applied onto the midvolar
fruits are widely used in cosmetic formulations. It is suggested that forearms of six volunteers at a dose of 2 mg/cm. After determined
AHAs reduce the calcium ion concentration in the epidermis thus time points, the stripping method was conducted and the sunscreen
promoting cell growth and differentiation giving rise to younger agent was assessed by HPLC while the SPF (sun protection factor) of
looking skin[42]. Glycolic acid is used in many cosmetic products as the formulations was determined in human volunteers in
exfoliant and moisturizer. It helps in reducing excessive epidermal accordance with the Australian standard. The results indicated that
keratinization which in turn is useful in reduction of facial lines. But skin accumulation of OMC in MLVs was significantly greater than in
it is irritant in nature causing burning at required concentrations. the o/w emulsion and SUVs. Furthermore, SUV's penetration into
This drawback can be overcome by liposomal encapsulation. the deeper skin layers was significantly greater than MLV's and that
Perugini et al. formulated glycolic acid liposomes with and without of a conventional o/w emulsion. Also, higher amounts of OMC were
chitosan by reverse phase evaporation method. They investigated recovered from the upper layers of the stratum corneum than from
the deeper layers in all the formulations tested. Finally, the SPF of
the interaction between liposomes and chitosan. The results showed
the liposomes containing OMC was greater than that of the control
that liposomes were suitable to modulate glycolic acid release and
lotions at a similar concentration of OMC[50].
that the best condition to achieve this control was obtained by 5:1
glycolic acid/lipid molar ratio. Further significant release control In a similar study, the photostability of avobenzone was improved in
was obtained by addition of chitosan into the liposomes[43]. presence of UVB filter octylmethoxycinnamate, when it was
encapsulated in liposomes, with a degradation percentage of 22.07
Similarly, salicylic acid (beta-hydroxy acid) which is commonly used % against 32.96 % of the non-encapsulated avobenzone[51].
to treat acne has also been used in anti-ageing creams. Liposomes
were prepared by the conventional thin film hydration technique as Peptides
described by Bangham. The liposomal encapsulation of salicylic acid
helped in overcoming its side effect of causing irritation[44]. Peptides have been widely used in anti-wrinkle creams. They reduce
fine lines and wrinkles and result in overall improved appearance of
Depigmenting agents photo aged skin. Shahi et al. encapsulated Palmitoyl hexapeptide and
Vitamin E acetate in liposomes by ethanol injection method for
Melasma or hyperpigmentation is a common disorder observed in improving topical delivery. They optimized the formulation by
middle-aged women. The use of hypopigmenting / skin lightening factorial design approach and developed stable and homogeneous
agents have thereby received attention. liposomal dispersion and lipogel with a controlled drug release
Hydroquinione has been used for decades as a skin lightening agent. profile upto 24 hours[3].
It has been shown to cause reversible hypopigmentation in man and Marketed liposomal formulations
animals. However this drug is susceptible to oxidation due to its
photosensitive characteristics. The liposomal formulation of Capture was the first anti-ageing liposomal cream launched by
hydroquinone helped improve its stability[45]. A United States Christian Dior in 1987 with claims that it can reduce the sign of
patent describes a cosmetic composition containing hydroquinone wrinkles. Capture liposomes penetrate beneath the stratum
and kojic acid incorporated into liposomes. The combination helps corneum and carry their ingredients into living cells, restoring the
in obtaining synergistic skin-lightening effect with reduction in membrane's fluidity. Among the ingredients in Capture Complex are
undesired side effects[46]. water, thymus extract, collagen peptides and elastin peptide[53].

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Lipo C TM by Lippomix is an anti-ageing liposomal cream which In the 1980’s L’oreal introduced its patented technology “Action
contains active vitamin C, vitamin E, coq10 and zinc. It claims to Liposomes” in French market. It was launched as the star product
minimize the appearance of cellulite while helping to tone and firm costing three times the cost of a basic moisturizer. Similarly L’oreal
sagging skin. Lipogest, a natural balancing cream, is a similar Eye defence which is an under eye cream based on liposomal
product by Lippomix[54]. technology, claims to reduce puffiness, lines and dark circles.

Table 2: Clinical trials evaluating cosmeceuticals agents[52]

Agent Clinical Indication Study Type Number of Results
patients
Oligopeptide Wrinkles, skin ageing OL, Cl 90 80% reduction in wrinkles
Peptide Primers Wrinkling OL, Cl 14 57% of patients improved

Transforming growth Wrinkling DB, R 32 87% of patients improved

factor / TGF-β1
(polypeptide)
Pal-KTTKS ( palmitoyl- Wrinkling DB, R 49 37% less wrinkle volume
pentapeptide) Winkling, fine lines OL, Cl 92 13% length reduction
Abbreviations: OL: open-label; CL: closed-label; DB: double blind; R: randomized.

Table 3: Marketed liposomal cosmetic formulations [21],[55],[56]

Product Manufacturer Key ingredients
Capture Christian Dior Thymus extract, collagen and elastin peptides

Effect du Soleil L’Oréal Tanning agents in liposomes

Liposome aktions gel Madame Nanette Biocosmetic Aloe vera, thymus extract
Future Perfect Estée Lauder Vitamin E, A, cerebroside,

Aquasome LA Nikko Chemical Co Liposomes with humectants like glycerine, sorbitol

Eye Perfector Avon Soothing cream with peptides to reduce eye puffiness
Royal jelly lift concentrate Jafra cosmetics Sunflower) Sprout Extract, Wintercherry and Lotus
flowers, Larrea Divaricata Extract
Revitalift L’Oréal Pro-Retinol A
Formule Liposome Gel Payot (Ferdinand Muehlens) Thymoxin, hyaluronic acid

Symphatic 2000 Biopharm GmbH Thymus extract,

vitamin A palmitate
Natipide II Nattermann PL Preformed Liposomal gel
Inovita Pharm/Apotheke Thymus extract, hyaluronic acid, vitamin E

CONCLUSION 5. B. Sharma and A. Sharma Future prospect of nanotechnology in

development of antiageing formulations Int J Pharm vol no 3 p.
Reported literature indicates that Liposomes are efficient colloidal 2012;4:57-66.
carriers for the delivery of therapeutics into skin. Due to the striking 6. Kohl E, Steinbauer J, Landthaler M, Szeimies RM. Skin ageing.
similarity between liposome components and skin lipids, they are safe Journal of the European Academy of Dermatology and
and effective. In addition to delivering the drug in higher concentration Venereology:JEADV. 2011;25(8):873-84.
into skin layers, they enhance skin hydration making them an ideal 7. Y. Moon, E.-Y. Yim, G. Song, N. H. Lee, and C.-G. Hyun, “Screening
vehicle for anti-ageing remedies. Studies on liposomes have been widely of elastase and tyrosinase inhibitory activity from Jeju Island
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