International Journal of Cosmetic Science, 2008, 30, 1933

Review Article

Novel cosmetic delivery systems: an application update

V. B. Patravale and S. D. Mandawgade
Department of Pharmaceutical Sciences and Technology, University Institute of Chemical Technology, Mumbai 400 019, India

Received 20 February 2007, Accepted 27 September 2007

Keywords: cosmetic delivery systems, encapsulation, nutracosmetics, personal care, skin care

Synopsis World consumers are nowadays more focused on their health and appearance. This trend is creating heightened demand for products formulated with natural and nutraceutical ingredients. Functional ingredients and innovative delivery systems are driving the new product development in the eld of cosmetics. A signicant number of innovative formulations are now being used in personal care with real consumer-perceivable benets and optimized sensory attributes, resulting in an economic uplift of cosmetic industry. In fact, the U.S. market alone for novel cosmetic delivery systems has been projected to be more than $41 billion for the year 2007. Novel cosmetic delivery systems reviewed here possess enormous potential as next-generation smarter carrier systems. Resume Les consommateurs du monde entier portent ` aujourdhui une plus grande importance a leur ` sante et a leur apparence. Cette tendance creee une demande accrue de produits formules avec des ingredients naturels et nutraceutiques. Les ingredi` ents fonctionnels et les systemes de liberation
Correspondence: Vandana B. Patravale, Reader in Pharmaceutics, Department of Pharmaceutical Sciences and Technology, University Institute of Chemical Technology (UICT), N. P. Marg, Matunga, Mumbai 400 019, India. Tel.: +91 022 24145616 Extn. 425; fax: +91 022 24145614; e-mail: vbpatravale@udct.org

` innovants sont a la base du developpement de nou veaux produits dans le domaine des cosmetiques. Un nombre signicatif de formulations innovantes sont maintenant utilisees dans les soins personnels avec un benece consommateur reellement percu et ` des attributs sensoriels optimises, ce qui conduit a un accroissement economique de lindustrie cosme tique. En fait, le seul marche US pour les nouveaux ` ` systemes de liberation a ete estime a plus de 41 ` milliards de $ pour 2007. Les nouveaux systemes ` de liberation cosmetique presentes ici possedent un potentiel enorme en tant que prochaine generation ` de systemes vecteurs plus sophistiques. Introduction World consumers are now focused on their health, well-being and appearance more than ever before. Terms such as natural, organic, no articial preservatives and no animal ingredients are drawing formidable attention. This trend is creating heightened demand for products formulated as cosmeceuticals with natural and nutraceutical ingredients. Functional ingredients and innovative delivery systems are driving the new product development arena. Nutracosmetics is an emerging class of health and beauty aid products. They combine the benets of nutraceutical ingredients with the elegance, skin feel and delivery systems of cosmetics. Nutracosmetics and cosmeceuticals thus differ in the origin of their functional ingredients. Nutraceutical ingredients formulated in cosmetic delivery systems

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constitute nutracosmetics, whereas cosmeceuticals are cosmetics formulated with pharmaceutical-type ingredients. Today, consumers worldwide are looking for personal care products that supply multiple benets with minimal efforts. They also expect the latest technology advances to be incorporated into innovative formulations. Faced with these trends, formulators strive to develop highly differentiated multifunctional products that focus on treatment as well as aesthetics. A signicant number of novel products are based on a new generation of active ingredients. With these emerging actives, come a range of formulation challenges that includes stability control and the complications of combining several actives into a single cosmetic product. As a discipline that concerns with the treatment of non-pathological skin, modern cosmetology is increasingly alternating with dermatology. To obtain skin care formulations with real consumer-perceivable benets and to optimize sensory attributes, formulators are resorting to technology that until recently was exclusively used in pharmaceutical products. These special delivery systems are now being used in personal care formulations. In cosmetics, the main concern is to reach cutaneous cell while limiting the passage into the blood circulation. The objectives of topical therapy can therefore be classied into two major areas: 1. To modulate or assist the barrier function of skin; 2. To administer an active ingredient to one or more skin layers or compartments while minimizing systemic involvement. Depending on the composition, a vehicle is used to exert mainly ve types of effects on the skin cleansing, decoration, care, hydration and protection. Delivering active substance to the targeted site requires the right concentration of actives in the formulation to achieve the optimal release rate and desired distribution of active substances between the vehicle and target site. A cosmetic care product has to be developed and whenever this is the case, various issues and aspects have to be considered such as site and area of application, sensory and optical properties, state of matter, actives and nal product storage stability and packaging. Cosmetic delivery systems Encapsulation techniques are most widely used in the development and production of improved deliv-

ery systems. Some of the important novel cosmetic delivery systems are discussed. Vesicular systems Following are the promising vesicle delivery systems in cosmetics: Liposomes; Silicone vesicles and matrices; Multi-walled delivery systems. Liposomes Liposomes are the most widely known cosmetic delivery systems. These are articial spherical submicroscopic vesicles with diameter between 25 and 5000 nm. Vesicles are composed inevitably of amphiphilic molecules. Their centre consists of an aqueous cavity, which is encapsulated by one or more bimolecular phospholipid sheets, each separated from each other by aqueous layers. The polar head group forms the interface at both the external and internal surfaces of liposomal bilayers. The phosphatidyl moiety consists of two fatty acids, which are ester bridged to glycerol phosphate. The chain length of fatty acids (mainly C14, C16 and C18) and the degree of unsaturation (one or two bonds) may vary. The polar head group may be zwitterionic, negatively or positively charged [1, 2]. The intensity of the mechanical mixing needed to form liposomes from lipid bilayer sheets determines the dimensions and number of vesicle bilayers. Such liposomes are multilamellar, small unilamellar and large unilamellar vesicles. The type of head group and fatty acid nature of phospholipids determine physical stability of liposomes. Natural lecithins (egg or soyabean lecithin) or synthetic lecithin (di-palmitoyl lecithin) are mostly used. The most common lecithin is mixture of phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, phophatidylserine and phosphatidic acid. Depending on the nature of components, which form their envelope, whole series of name other than liposome have been given to the commercial products [3, 4]. Liposomes are articial phospholipid membranes that can facilitate the passage of active principles across the stratum corneum. After the fortuitous observation that phospholipids exhibit a marked afnity for some classes of avonoids, a new series of compounds denominated as

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phytosome has been developed by complexation with polar botanical derivatives such as catechin, quercetin, escin and glycyrrhetinic acid. From the chemical viewpoint, phytosomes are complexes between a pure phospholipid and pure active principles. Niosomes are non-ionic surfactant vesicles fabricated from polyoxyethylene alkyl ether, polyoxyethylene alkyl ester or saccharose diester. The oil spreads uniformly over the surface of the skin; vesicles penetrate the stratum corneum in fractioned form while the water of continuous phase evaporates. The result is a special sensation to touch, freshness, even essence, hydration and a feeling of protection because of the oily lm. If the envelope is made of sphingolipids, vesicles are named sphingosomes [57]. Marinosomes (Bordeaux, France) are liposomes based on a natural marine lipid extract containing high ratio polyunsaturated fatty acids like, eicosapentaenoic acid (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3). They are not present in normal skin epidermis. However, they are metabolized by skin epidermal enzymes into anti-inammatory and anti-proliferative metabolites that are associated with a variety of benets with respect to inammatory skin disorders [8]. In one study, Marinosomes were prepared and characterized in conditions that mimic topical application in terms of pH and temperature. Further, preliminary freeze-fracture TEM observations concerning Marinosomes formulations in oil-in-water (O/W) emulsion showed that the membrane structures were mostly preserved even in the presence of surfactant. In parallel, the rst toxicology le indicated a good skin and eye tolerance towards Marinosomes. All these results allowed considering Marinosomes as potential candidates for cosmeceutical in view of the prevention and treatment of skin diseases [9]. Other related small vesicles having size around 20 nm, formed by a gellied polysaccharide hydrophilic core capable of capturing the active substances in the link of a network are termed as supramolecular biocarriers. Their central core is surrounded by crown of fatty acids attached to the core by a covalent bond. The whole is covered by an external sheet of phospholipids attached to the lipid crown by hydrophobic interaction with their polar heads facing the periphery. The hydrophilic actives are attached to the heart of the core, whereas the active
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lipophilic substances penetrate through the double lipid membrane [10]. Some important liposomal preparations having cosmetic potential are discussed [11, 12]. The skin care preparations with empty or moistureloaded liposome or niosome reduce the transdermal water loss and are suitable for the treatment of dry skin. They also enhance the supply of lipids and water to stratum corneum. Liposomal formulations would have an advantage that the active ingredient would be distributed optimally in the horny layer and also would acquire a certain water resistance. This has been illustrated by liposomally encapsulated radical scavenger tanning agents such as tyrosine and creams containing aloevera, a-hydroxy acids (glycolic acid), sun-protection formulations with UV absorbers. Liposome with anti-ageing complex such as face capture contains thymus extracts, collagen and elastin. Capture increases the cellular activity and rejuvenates the cells. Capture containing proteins and peptides form a part of the connective tissue and enhance the strength and tone of the skin. Les vitamins is a day cream with liposome containing vitamin A, vitamin B2, vitamin B5 and vitamin E. The cream assists in the skin regenerative process and is helpful in removing the visible signs of ageing. Liposome stability may be referred to in terms of leakage of contents, presence of oxidation products or change in particle size because of aggregate formation and fusion. Enclosing them in a gel matrix can protect liposomes. The stability of liposome in gellied aqueous or hydro-alcoholic environment ranges between 2 and 3 years at a temperature 425C. Stable liposomes can also be prepared by polymerization of phospholipids, coating them with a mixture of collagen and polysaccharide, albumin or c-globulin. Polyethylene glycol (PEG) polymer chains of various lengths can be covalently coupled to lipids. Such liposomes are called stealth liposomes or sterically stabilized liposome. Degradation of liposomes is largely related to oxidation and hydrolysis. Oxidation of liposome can be avoided by using phospholipids with fully saturated acyl chains (hydrogenated soyabean). Hydrolysis of the ester groups can be avoided by keeping the pH values near 4.56.5. However, they remain stable only for a few months, if dispersed in a lipid-rich solution containing surfactant [13]. Some of the specialized liposomal preparations are as follows.

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Ultrasomes Ultrasomes are specialized liposomes encapsulating an endonuclease enzyme extracted from Micrococcus luteus; the enzyme recognizes the sun damage to the skin and initiates removal of damaged DNA. Photosomes Photosomes are incorporated in sun-care product to protect the sun-exposed skin by releasing a photo-reactivating enzyme extracted from a marine plant, Anacystis nidulans. Photosomes on light activation reverse the cell DNA damage, reducing immune suppression and cancer induction. AOCS liposome Asymmetric oxygen carrier system (AOCS) liposomes are designed to carry oxygen into the skin. These vesicles are composed of peruorocarbon core surrounded by a monolayer of phospholipids, followed by a bilayer system. Peruorocarbons are excellent carriers of oxygen and so this system is used to transport molecular oxygen into the skin. Yeast-based liposomes Yeast cell derivatives repair, soothe and oxygenate the skin. In its liposomal form, it stimulates dermal broblasts and provides a feeling of well-being. Incorporation of vitamin C into the cell increases signicantly when liposomes are used as a vehicle [4, 14]. Silicone vesicles and matrices Silicones in physical association with various active ingredients can function as delivery vesicles for the actives. In the most basic example of this concept, aluminium zirconium tetrachlorohydrex GLY, an active ingredient used in anti-perspirant applications was suspended in a vesicle based on volatile silicones. The anhydrous vesicles reduce stickiness and protect the activated salts from hydrolysis. The active is released when the volatile silicone evaporates. This approach has been expanded to ingredients such as fragrances and conditioning ingredients. Based on in vitro and in vivo sun protecting factor (SPF) evaluations, it was determined that stearyl dimethicone contributed to increased SPF compared with the formulations without stearyl dimethicone. High values of thixotropy for the stearyl dimethicone allow the product to be evenly distributed on the skin, improving sun protection by forming uniform homogenous

lm. Silicones have a long history of use in hair care, where they are recognized for their ability to provide improved conditioning, shine, manageability, reduced yway and number of other benets. The polymer based on hydroxyl ethyl cellulose cationic modied and hydroxyl propyl guar hydroxyl propyl trimonium chloride have various benets including wet combing and hair manageability. The addition of certain silicone polymers to the above-mentioned systems has been found to improve conditioning performance. However, the synergy between these two types of materials has been only recently demonstrated. Several siliconebased technologies illustrate the synergistic properties of silicones with a variety of personal care actives via physical association. These technologies offer a wide scope for a range of innovative personal care applications [15, 16]. Induction of silicone polyether into nanomicron- to submicronsized vesicular structures provides excellent stability in aqueous medium. These are called assembly-required vesicles. Actives that can be delivered by silicone-based vesicles are [17]: 1. Conditioning agents such as vitamin A, vitamin E acetate and lanolin oil, humectants such as lanolin alcohol, cetearyl octanoate and sodium stearoyl lactylate, colorants; 2. Emollients such as mineral oil, jojoba oil and polydimethyl siloxane. Common silicone uids such as dimethicone are well known to cosmetic formulators. A general property of silicone polymers is their high permeability. The permeability of silicones makes them suitable for controlled release applications and for this reason they are used widely in transdermal delivery systems. Cross-linked silicones such as elastomers and adhesives are a relatively new class of cosmetic raw materials that have utility in delivery systems for active ingredients [18]. Silicone elastomers are cross-linked and the interconnections between polymer chains make the elastomers solid material. Because of this structure, an active ingredient can be trapped in the matrix and will not separate even if the active ingredient is not soluble in the elastomer matrix. Most of the active ingredients now can be loaded into an elastomer matrix. Formation of silicone polymer systems is based on different cross-linking schemes, viz. 1. Condensation of a silica derivative with hydroxyl-terminated silicone polymer;

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2. Mixing the active ingredient with the silicone polymers before cross-linking; 3. Swelling the cross-linked silicone matrix with a suitable solvent and using this solvent to carry the active ingredient into the matrix. One example of controlled release that has been used commercially is the incorporation of fragrance into a silicone elastomer that is highly swollen with silicone uid. The use of such a silicone elastomer blend to modulate the release rate of fragrance has been reported [19]. Combining the active ingredient with a silicone surfactant can increase the release rate. Multi-walled delivery systems The multi-walled delivery system (MDS) is based on a combination of structured vesicle-forming materials and high shear processing. It provides exceptional long-term stability to cosmetic skin treatment products. MDS is analogous to the structure of membrane lipid found in the intracellular matrix and made up of non-phospholipid amphiphilic molecules (oleic acid, derivatives of polyglycerols, amino acid residues). Stability of these types is predicted by zero-order kinetics. When they are produced, MDS vesicles form ve to seven bilayer walls. MDS gives stability to liposomes but by combining hydration and delivery, MDS also nourishes and protects the skin, bringing the formulator closer to optimizing product performance [20]. Derivatives of essential fatty acids (EFAs) and ceramides dene todays MDS [21]. EFAs bind large volumes of water and form exible membranes that smoothen the stratum corneum. MDS can be engineered to permeate the stratum corneum or to remain on top of the stratum corneum, offering a truly delayed release effect as the multiple bilayers release their contents in response to decreasing levels of moisture on the skin. This forms effective delivery of sunscreens. Mixture of glyceryl distearate, polyoxyethylene stearyl ether and cholesterol could be used as a wall-forming material to prepare MDS vesicles. These cyclomethicone-loaded MDS are stable over a period of time and ready for incorporation into any desired number of formulations. A 30% w/w petrolatum MDS was prepared. At this concentration, petrolatum is a skin protectant. The MDS allows for petrolatum to be applied without occluding the skin. Small amino acid peptide chains have been encap 2008 The Authors. Journal compilation

sulated using MDS approach and formulated into a cream. Encapsulated peptide fraction showed no degradation over a period of 70 days and was also found to enhance the percutaneous absorption of peptide in human skin [22]. Emulsions Following are the different emulsion delivery systems used in cosmetics: Microemulsions; Liquid crystals; Multiple emulsions; Nanoemulsions; Pickering emulsions. Microemulsions Microemulsions are stable, transparent (or translucent), dispersions of oil and water stabilized by an interfacial lm of surfactant molecules and having diameter <100 nm. Microemulsion formation usually involves a combination of three to four components water, oil, surfactant/s and co-surfactant/s. The surfactants chosen are generally those in the non-ionic group because of their good cutaneous tolerance and balanced lipophilic and hydrophilic property. The most important role of co-surfactant in the formation of microemulsions is to increase interfacial uidity and to modify the Hydrophilic-Lipophilic Balance (HLB) of surfactant to optimal value. Thus, their combination is more effective than a single surfactant. Factors affecting stability of microemulsions include interfacial tension, interfacial curvature, entropy and uidity. In microemulsions, the active is solubilized rather than suspended as in the vesicles and is available for immediate absorption, generally more rapidly and effectively. Microemulsions are easy to manufacture as they form spontaneously without high shear equipments. Their optical transparency and low viscosity ensure that they are of good appearance, easy to handle and pack. Microemulsions are preferred to be used in moisturizing formulation because they provide occlusivity and full criteria for aesthetic appearance, ease of removal from container, ease of application and adherence to treated area without tackiness. Carotenoids formulated in a microemulsion are employed for treatment in skin cancers. Cosmetic microemulsion containing di-decanoyl glycerol is used to increase melanin content of melanocytes

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thereby increasing pigmentation of skin. Moisturizing effect and penetration of vitamin E is enhanced when employed in a microemulsion. The efciency of tri-decyl salicylic acid was increased when incorporated in microemulsion as an anti-ageing composition. Benzotriazoles, bisesorecinyl triazine and S-triazine have been incorporated in microemulsion for photo-protective efcacy. Microemulsion containing ascorbyl palmitate effectively prevents UV-A-induced lipid peroxidation [23, 24]. A new multifunctional silicone quaternary polymer microemulsion for hair care offers conditioning as well as protection from heat, improved colour retention, enhanced body and volume and also the product clarity [16]. Liquid crystals Liquid crystalline phase is thermodynamically stable and represents a state of incomplete melting. Liquid crystals are mainly of two classes thermotropic liquid crystals (smetic and nematic type) and lyotropic liquid crystals. Liquid crystals exhibit birefringence and dichromism and hence enhance the cosmetic appeal because of the coloured appearance of the preparations into which they are incorporated. Liquid crystals form multilayers around the emulsion droplets, decreasing the van der Waals energy and increasing the viscosity which increases the emulsion stability. These multilayers act as rheological barriers to coalescence. Lipophilic materials such as vitamins, incorporated into liquid crystalline matrix, are protected from both thermal and photo-degradation. Emulsions containing liquid crystals have been observed to have a rate of active release much slower than those without this stabilizing component. This effect is because of multilayer structure of liquid crystalline material around droplet, which effectively reduces the interfacial transport of the dissolved actives from within the droplet. For example, timed release of vitamin A palmitate containing liquid crystals dispersed in water-based gel [25]. Multiple emulsions Multiple emulsions are emulsions in which globules of the dispersed phase encapsulate smaller droplets, which in most of the cases are identical with continuous phase. The two major types of multiple emulsions are W/O/W in which internal and external aqueous phases are separated by an

oil layer and O/W/O in which water separates the two oil phases. In cosmetics, the most widely used type is W/O/W. Although multiple emulsions especially W/O/W systems have potential applications in controlled release systems for delivery of the active ingredient, their use has been limited by lack of stability. Multiple emulsions consist of W/O and O/W emulsions and requires at least two stabilizing surfactants, a low HLB one forming primary emulsion and a second, higher HLB surfactant to achieve the secondary emulsication. Primary emulsiers are decaglycerol decaoleate, mixed triglycerol trioleate and sorbitan trioleate. Secondary emulsiers include polysorbates and poloxamers for W/O/W emulsion [26]. Multiple emulsions are thermodynamically unstable systems. Principal modes of emulsion breakdown involve coalescence of internal or external droplets, expulsion of internal droplets, osmotic swelling or shrinking [27]. Stability of the multiple systems can be improved by forming a polymeric gel in either the internal or external aqueous phase. Two principle hypotheses were proposed for the mechanism of transport of solute from multiple systems. In the rst hypothesis, the active substance is released in the internal phase by virtue of the rupture of multiple oily globules. This rupture takes place either by shearing (induced by rubbing the preparation on the skin) or by swelling of internal phase. In the second hypothesis, the encapsulated active substance diffuses through the oily membrane. This would be dependent on several factors like partitioning of actives, its permeability and diffusion rate through oily membrane, viscosity and thickness of interfacial lm, presence or absence of liquid crystals, particle size and its distribution [2830]. In cosmetics, multiple emulsions are useful when one wishes to prepare sustained release aerosol fragrances, prolonged skin moisturizers and protection of sensitive biologicals, personal care formulations for perfumes, skin lipids, vitamins and free radical scavengers [3133]. Polyaphrons are three liquid-phase dispersions, the internal phase being stabilized by encapsulation in a thin aqueous soapy lm. Polyaphrons exhibit foam-like character in which the oil-encapsulated cells aggregate to form stable polyhedral structures. Dispersions containing 97% of dispersed oil phase within a continuous structure that contains only 3% water could be achieved [28]. In another example, a ve-phase novel emul-

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sion consists of water, peruorinated oil and liquid crystal dispersed in a continuous silicone phase along with coarsely dispersed aqueous gel phase. Lipophilic actives can be incorporated into the liquid crystalline phase; hydrophilic actives can be dissolved in either of the two aqueous phases. Such systems can be used to incorporate two incompatible hydrophilic actives in different aqueous phases. Nanoemulsions Nanoemulsions consist of very ne oil-in-water dispersions, having droplet diameter smaller than 100 nm. Compared with microemulsions, they are in a metastable state and are very fragile systems by nature. Their structures depend on the process used to prepare them. They can be prepared by spontaneous emulsication such as phase inversion temperature (PIT) emulsication or phase inversion composition, or by using a high shear device, which allows a better control of the droplet size and large choice of compositions. The nanoemulsions are easily valued in skin care because of their good sensorial properties (rapid penetration, merging textures) and their biophysical properties (especially, hydrating power). They lead to a large variety of products from water-like uids to ringing gels. Lotions, transparent milks, crystal-clear gels with different rheological behaviours, visual aspects, richness and skin feel are allowed with nanoemulsions. A signicant improvement in dry hair aspect (after several shampoos) is obtained with a prolonged effect after a cationic nanoemulsion use. Hair becomes more uid and shiny, less brittle and non-greasy [34]. A great deal of effort is currently being put into the development of aqueous-based nail lacquers. The nail lacquers are based on aqueous polymer emulsion and contain in addition, oxyalkylene glycols and selected oils, as plasticizers. These nail lacquers reportedly adhere well to the nails, are characterized by good gloss, exhibit good water resistance after drying and do not have any solvent odour [35]. According to a patent application assigned to Advanced Genetic Technologies Corp., protein-adherent polymers with hydroxyl-substituted aromatic groups can be used to increase the adhesiveness and durability of nail polish compositions [36]. Nails are not porous although they permit the penetration of externally applied materials through nail plate, including moisture that helps
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maintain exibility [37, 38]. The moisture content of nails is less than half that of the stratum corneum and total lipid content is <1%. Considerable efforts are being made in Japan to develop watercontaining nail enamels to address the dry/brittle nail problem. In a work by Yamazaki et al. [39] on the development of new water-in-oil (W/O) emulsion type nail enamel using human sections, a series of model experiments were performed conrming that moisture is essential for exible and non-brittle nails. The researchers developed a new, nitrocellulose containing W/O emulsion nail enamel, which kept the nails in good condition. Ultraset Limited Corp. has come up with a quickdrying, photo-reactive nail polish coating composition that cures quickly on exposure to natural light. The resulting product is compatible with commercially available nail polish of any colour. It is also compatible with every-day chores because it is insoluble in water [40]. Pickering emulsions Pickering emulsions have been a laboratory curiosity since their discovery almost a century ago. Recent technological advances in this eld have resulted in the introduction of amphipathic nanoparticles that enable the production of surfactantfree, particle-stabilized emulsion. It has been revealed that the emulsier-free O/W pickering emulsion can be formed in which the stabilizing particles are zinc oxide or titanium dioxide that have been coated with aluminium stearate or dimethicone and aluminium hydroxide or silicon dioxide [4143]. The ultra-ne amphiphilic particles are dened as having particle sizes <200 nm. The specications of the patents disclosed that these formulated emulsions are characterized by excellent skin tolerability and exhibit higher effectiveness in sunscreen formulations. The inventors also reveal that these particle-stabilized emulsions are remarkably stable in the presence of electrolytes and this makes it possible to design systems containing both astringents and anti-microbials. These stable compositions can also contain nonamphiphilic pigments such as hydrophobically modied titanium dioxide [44, 45]. Polymeric moisturizers can also be included [46]. One drawback of particle containing emulsion is dull or dry impression on the skin, which can be overcome by the addition of cyclodextrin preferably b- and a-cyclodextrin [4749].

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Particulate systems The particulate delivery systems used in cosmetics include: Microparticulates; Porous polymeric systems; Nanoparticulates; Cyclodextrin complexes. Microparticulate systems Microparticles are solid polymeric particles falling in the range of 0.11000 lm and include microcapsules and microspheres. In general, microparticles are used in cosmetics to avoid incompatibility of substance, reduce odour of actives and for protection of substances prone to oxidation or action by atmospheric moisture. Listed below are some of the applications of microcapsules in controlled delivery. 1. Microcapsules containing sun lters such as octyl methoxycinnamate, octyl salicylate; 2. Depilatory pastes containing microencapsulated enzyme for protection against surface active agents. (e.g. Sodium Lauryl Sulphate (SLS)); 3. Skin tanning agent containing dihydroxyacetone (DHA) and glycerine in separate compartments within a microcapsule; 4. Microcapsule with encapsulated oils like, mineral oil, vegetable oil, isopropyl myristate, isopropyl palmitate contained in cleansing creams; 5. Skin depigmentation products containing microencapsulated anti-oxidants such as tocopherols, which will prevent lipid peroxidation in the skin. Nylon microspheres are being used in cosmetic make-up and skin care products because of the feel and skin adhesion they impart, because of their particle size and narrow particle size distribution. Chemical inertia of nylon microspheres allows them to hold hydrophilic and lipophilic ingredients including vitamins, sun lters, moisturizers, fragrances and many other actives such as retinyl palmitate, d-panthenol, ascorbic acid, tocopheryl acetate and dimethicone. Nylon microspheres containing 4050% water can function as a delivery system when incorporated in a moisturizing lipstick. It can also avoid exudation observed in lipsticks. DHA-impregnated nylon microspheres as a self-tanning formulation showed increased stability. Microspheres loaded with vitamin E showed enhanced concentration of vitamin E in the epidermis because of continued contact with skin and microspheres, slow release of vitamin from the

particles and protection of vitamin E from chemical interactions before absorption. The nylon microspheres can be used in combination with either or both organic chemical and particulate mineral sun lters to reduce lter concentration while retaining effectiveness [50]. Egg albumin microspheres of size 222 lm, containing vitamin A (15.7 0.8%) were used to prepare O/W creams. The in vitro and in vivo drug release of a microencapsulated vitamin A cream was studied and compared with a non-microencapsulated vitamin A cream. The in vitro study showed a prolonged release of vitamin A, the relative bioavailability of the microencapsulated formulation being 78.2 7.3% [51]. LipoPearl (Lipo Chemicals Inc., Paterson, NJ, USA) represents standardized line of pearlescent beads containing emollient oils and vitamins that enhance the tactile and visual appearance of cosmetic and personal care products. The average size is 10002800 lm. A variety of LipoPearl products are readily available. Agar LipoSphere (Lipo Chemicals Inc., Paterson, NJ, USA), derived from a renewable marine source, offers a wide range of encapsulation possibilities. These spheres provide the visual effects, which were previously available only with gelatin capsules while offering the same ease of formulation. Agar LipoSphere leaves little or no residue upon rubout. The average size is between 500 and 4000 lm. Lipobead (Lipo Chemicals Inc., Paterson, NJ, USA) is a uniform spherical semi-solid matrix of lactose, microcrystalline cellulose and hydroxypropyl methylcellulose, coloured by pigments. Lipobead (Lipo chemicals Inc., Peterson, NJ, USA) is an ideal, simple carrier system for active ingredients in creams, lotions, gels, body cleansers, shampoos, conditioners, hair gels and foot care products, where an exciting visual effect is desired (www. lipochemicals.com). Botanical microspheres such as Elespher of natural origin are composed of algae extract, which forms spheres containing a system of internal canals. Release of actives occurs by diffusion from sphere or by breaking when applied to the skin. They can be even coloured to achieve a pleasing visual effect [52]. Unispheres are an alternative to liposomes in preparations like shampoos containing high concentration of surfactants. These are small, coloured cellulose beads that hydrate and swell in aqueous media and disappear when rubbed into the skin leaving behind no shell.

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Porous polymeric systems Porous polymeric systems utilize microentrapment technology wherein the particles have an open, porous structure compared with the continuous shell structure associated with microencapsulation, which results in sustaining the activity of the active ingredients over longer periods of time. The spheres can be programmed to release the entrapped active ingredient to the skin in a controlled time release pattern or a pre-programmed manner through the use of several different triggers such as rubbing or pressing the system after it has been applied to the skin, elevating the skin surface temperature, introducing solvents such as water, alcohol, perspiration for the entrapped material. Entrapment systems can control the release of actives onto the epidermis with assurance that the actives remain primarily localized and do not enter the systemic circulation in signicant amounts, thus reducing toxicity while maintaining efcacy. They have high pay load capacity and can hold up to 5060% of solid, semisolid or liquid material, which can comprise aqueous hydrophilic material as well as oils and lipophilic materials. Sorption-based polymer systems provide optimal medication over a moderate period of time and hence overcome the problems like rashes or other energic responses. Signicant reduction in undesirable properties such as, oiliness, greasiness, tackiness, stickiness or undesirable odour and feel of ingredients was also seen. Shelf-life and product stability can be prolonged without the use of chemical preservatives as bacteria are too large to enter the entrapped material. Microsponges are polymeric delivery systems consisting of porous microspheres, each microsphere consisting of a myriad of interconnecting voids within a non-collapsible structure with a large porous surface. The porous sphere polymers vary in diameter from 5 to 300 lm. A 25 lm sphere can have up to 3000 mm of pore length providing a total pore volume of about 1 ml g)1. The highly compartmentalized nature of these materials lends them a very high internal surface area and high-level payload. Depending upon their particle size, these porous systems can be divided into microporous microbeads (particle below 50 lm) and microporous macrobeads (particle range of 100200 lm). These porous sphere polymers consist of a polymeric membrane that holds
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together the solid nanoparticles, which compose the core of the sphere. The outer membrane is interrupted by a multitude of pores that allow entrapped active to ow out of the sphere [53]. Microsponge particles are made by free radical suspension polymerization technique. This approach involves the synthesis of a dispersed phase made up of a monomer, cross-linkers, an initiator, water immissicible active ingredient/s and surfactants to promote suspension. Once polymerization is completed, the resultant solid particles are recovered from suspension. Release rate and diffusion of entrapped material from such system can be modied by altering the particle size, pore diameter, volume and monomer composition [54]. These systems have a myriad of applications. Melanosponge-a containing genetically engineered melanin is designed to distribute melanin over the skin surface, providing full spectrum sun protection by blocking UV-B and UV-A light. In anti-acne formulations, a reduction in the skin irritation potential with increased efcacy was observed when benzoyl peroxide was entrapped in a microsponge system. Anti-inammatory activity of hydrocortisone could be sustained with reduction in skin allergy responses and dermatoses. In anti-dandruff products, the unpleasant odour of zinc pyrithone and selenium sulphide was reduced. Irritation was lowered, whereas safety and efcacy were found to be extended. All day treatment and symptomatic relief of fungal problem have been achieved through such systems. Reduced allerginicity was observed when insensitizing ingredients are entrapped in microsponge systems, as in the case of cinnamic aldehyde [55]. Another polymeric sorption system prominent in cosmetic delivery is Polytrap. These are highly cross-linked methacrylate copolymer powders, which are capable of sorbing up to four times their weight of lipophilic and hydrophilic liquids while maintaining owable powder form. The systems can sorb liquid dispersions, emulsions and solids that can stay long enough to be sorbed by and in the form of polymer aggregate [1, 53]. Chronospheres are polyurethane/acrylate polymer (PAP)-based powders. PAP powders with pre-loaded actives represent a nished topical product with controlled/sustained release capabilities. By adding the active at the liquid oligomer precursor stage and then converting the molecular solution to a solid microparticulate matter without using heat or solvents, consistent active

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levels are assured and the degradation of sensitive material is avoided. Such powders are currently available containing benzocaine, glycerine, allantoin, salicylic acid and collagen as active ingredients [56]. Nanoparticulate systems Nanoparticulate systems include nanospheres and nanocapsules and can be dened as submicron colloidal systems having a mean particle diameter of 0.0031 lm. Nanocapsules differ from nanospheres in that the former is a reservoir type of system, whereas the latter is a matrix system. Polymer composition for both is identical and includes biodegradable synthetic polymers like polyamides, cross-linked polysiloxanes or modied natural products such as, gelatin and albumin. The active ingredient in nanocapsules and nanospheres can be incorporated in different patterns; dissolved in the nanosphere matrix, adsorbed at the nanosphere surface, dissolved in the liquid-phase nanocapsules, adsorbed at the nanocapsules surface. In case the active is adsorbed on the carrier surface, the active release from polymeric nanoparticles is biphasic with an initial burst phase followed by sustained release. An ideal delivery system for water-based skin product would be a product that is completely washable with water; yet, the functional ingredients remain in contact with the skin to perform their pharmacological action. These two completely opposite performance criteria can be achieved by applying a delivery system that incorporates bio-adhesive nanospheres. The nanospheres can be surface modied to promote adhesion and hence deposition on body surfaces in rinse-off products. High cationic charge density improves the deposition of the nanospheres onto the target site and prevents them from being diluted or washed off during the rinse process. Such delivery technology enhances adhesion mostly because of the fact that the functional ingredient is retained in a solid structure that has a high surface area per volume with presence of charges and moieties on the nanospheres surfaces. The sustained release of fragrance at 0.5% was tested with free and encapsulated in highly cationic nanospheres. The results indicated that three times as much fragrance remained on the skin after 2 h, when the fragrance was encapsulated inside the nanospheres [57].

Another important system is solid lipid nanoparticles (SLNs). These represent a particulate dispersion of solid spherical particles consisting of hydrophobic core of triglycerides or fatty acid derivatives surrounded by a layer of phospholipids. The advantage of SLNs over polymeric nanoparticulate systems is the absence of harmful additives required for polymerization and biodegradability of physiological lipids. When compared with liposomes, they have better stability against coalescence because of the solid nature and reduced mobility of incorporated active molecules, preventing the active leakage from the carrier. SLNs possess some features, which make them promising carriers for cosmetic applications: 1. The protection of labile compounds against chemical degradation (e.g. for retinol and tocopherols). 2. Depending on the produced SLNs type, controlled release of the active ingredients is possible. SLNs with a drug-enriched shell show burst release characteristics whereas SLNs with a drug-enriched core lead to sustained release. 3. SLNs act as occlusive, they can be used to increase the water content of the skin. 4. SLNs show a UV-blocking potential. They act as physical sunscreens on their own and can be combined with molecular sunscreens to achieve improved photo-protection. It can be remarked that SLNs with a desired degree of occlusion can be produced when the particle size is taken into account. The dependence of the occlusive effect on the particle size of SLNs is because of lm formation. An in vivo study showed that addition of 4% SLNs to a conventional O/W cream leads to an increase in skin hydration by 31% after 4 weeks. The application of SLNs as physical sunscreens and as active carriers for molecular sunscreens has also been investigated. Incorporation of molecular sunscreens in SLNs leads to synergistic UV-blocking effects. The amount of molecular sunscreen could be decreased by 50% while maintaining the protection level comparable with a conventional emulsion [58]. Dingler et al. reported that the incorporation of vitamin E into SLNs enhances the stability. The ultra-ne particles possess an adhesive effect. This leads to a formation of ne adhesive lm on the skin leading to occlusion and subsequent hydration. Hydration of the skin promotes penetration of actives and enhances their cosmetic efciency [59]. In a 1997 patent, De Vringer showed that the size

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of particles could change the occlusion factor. Lipoid microparticles are greatly inferior to lipoid nanoparticles in their occlusive effect and the addition of lipoid microparticles in a cream lowers the creams occlusivity, whereas the addition of lipoid nanoparticles in a cream raises the creams occlusivity. Nanospheres containing b-carotene and a blend of UV-A and UV-B sun lters were prepared. The results clearly show that the synergistic effect resulting from the combination of nanospheres and lters has an inhibitory effect on tyrosinase by cinnamic nature of the UV-B screening agent [60]. Cyclodextrin complexes Cyclodextrins (CDs) are cyclic oligosaccharides containing a minimum of six d-(+)-glucopyranose units attached by a (1 4) glucosidic bonds. The three natural CDs are a, b and c which differ in their ring size and solubility. Most of the molecules t into the internal CD cavity forming a complex and the resulting structure is called CD clathrates or inclusion complexes. a-CD typically forms inclusion complexes with both aliphatic hydrocarbons and gases. b-CD forms complexes with small aromatic molecules. c-CD can accept more bulky compounds like vitamin D. Complexation with CDs can bring about stabilization of the active ingredient against oxidative, photolytic and thermal degradation. It can keep the molecules in a more rigid form, inhibit occurrences of reactive conrmation (e.g. vitamin E and vitamin C phosphate included in hydroxylated cyclodextrin showed improved light stability compared with un-complexed form of the compound), isolates the molecules from environment and diminishes the incompatibilities (decreasing skin penetration of guest molecules by CD encapsulation thereby reducing undesirable side effects). Complexation with CD can mask the smell of mercaptan, inherent to many wave products, by reducing volatility of the thiol groups. The self-tanning agent di-hydroxyacetone with tyrosine, which increases production of melanin in the skin is an unpleasantly scented substance. Including CD in the formulation can eliminate this problem [61]. Empty CD complexes with polyunsaturated fatty acids in sebum prevent their oxidation and inhibit the free radical formation. It has therefore proved to be an efcient anti-acne agent, also reducing the infections and inammation. Aqueous solubility of minoxidil (compound stimulating
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keratinocyte growth and promote hair growth) can be increased through complexation with a-CD [62, 63]. Delivery devices Following different delivery devices in the cosmetic delivery are discussed. Iontophoresis; Cosmetic patches. Iontophoresis Iontophoresis is a virtually painless procedure that uses a mild electric current to deliver water soluble, ionized compounds into the intact skin and the underlying tissue. Iontophoresis has gained a great deal of attention during the last two decades for both systemic and topical delivery. It is particularly attractive for the delivery of low-molecularweight (<1000) hydrophilic solutes at the site of action [64]. It has been observed that for ionic molecules, the major contribution to the overall ux is because of iontophoretic delivery, whereas diffusive delivery and electro-osmosis make a relatively smaller contribution to ion ux [6567]. Iontophoresis is an active means to deliver active agent into the skin and to achieve enhanced cosmetic benets in a variety of skin disorders. Use of appropriate composition of electrical current and the active agent can provide superior results in the treatment of hyper-pigmentation, melasma, aged skin, acne scars [68], hypertropic scars [69, 70], cellulite and many other aesthetic disorders of the skin. A typical iontophoresis device consists of an electrical power source, electrodes and the active agent in an appropriate carrier (solution, gel or cream). There are several examples of uses of iontophoresis and electro-osmosis in cosmetics. Vitamin C is known to inhibit both melanin formation and oxidized melanin. However, vitamin C does not easily penetrate the skin. A controlled human study was carried out for 6 weeks with enhancer patch and magnesium ascorbyl phosphate (MAP) 3% gel. The data revealed a 50% mean reduction in spot size and a 60% decrease in pigment intensity within 42 days. In addition, signicant effects were noticeable after only 7 days of treatment. This effect was 300% better than the results attained by applying the MAP 3% passively onto the face without using micro-electronic currents [71].

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Schmidt et al. [72] have reported on treatment of post-acne scars using iontophoresis with 0.025% tretinoin gel. Tretinoin iontophoresis was found to be effective, non-invasive treatment of atrophic acne scars without causing disturbing side effects. Cosmetic patches The inuence of the pharmaceutical technology is apparent in the case of the cosmetic patches, not as simple cosmetic forms but as cosmetic delivery systems. Cosmetic patches today represent a convenient, simple, safe and effective way for cosmetic applications, using one of the most acceptable, modern and successful delivery techniques. In theory, cosmetic patches can be applied in most cases for the same use as classical cosmetic products, for example, wrinkles, ageing, dark rings, acneic conditions, hydration of specic areas, spider veins and slimming. In practice, several of the aforementioned applications have been investigated with very positive results and a high degree of acceptability from the consumers. There are several ways to categorize a cosmetic patch. It can be characterized from the patch form (matrix, reservoir), application for expected results (moisturizing, antiwrinkles), structural materials (synthetic, natural and hybrid), the duration of application (overnight, half-hour patch). Categories of functional cosmetic patches are anti-blemish patch, pore cleansers, pimple patch, eye-counter patch, antiageing patch, anti-wrinkle patch and lifting patch [73]. Power paper micro-iontophoretic patches equipped with integrated electrical cell and a

hydrogel interphase are intended for use on skin wrinkles. Human clinical study has shown that a single 20-min treatment using the patch resulted in a visible reduction of the number and depth of wrinkle under the eye and lasted for several hours. The short-term effect can be explained by the occurrence of a slight, sub-clinical inammatory response, which resulted in skin smoothening. The longer-term rejuvenation effects may have resulted from tissue stimulation, enhanced blood ow, improved respiration and increased cell turnover [74]. Future trends in cosmetic delivery Through the efforts of the cosmetic industry, liposomal and nanoparticle formulations for the skin have denitively been an economic success. Molecular biology has provided us with tools to identify and build genetic materials that can be used for the treatment of hereditary diseases. The efforts made to obtain a better understanding concerning the mechanisms of the novel formulations at the molecular and supramolecular level have led to new formulation processes and could open new prospects in the area of active delivery by means of encapsulated system. Controlled release will continue to play a large part in the efcacy of cosmetics. Some trends that the consumers are likely to see in the future include improved systems that release their actives via pH and temperature modulation. The liposomal dispersions have proved not only to be innovative and effective cosmetic delivery systems but also very successful for preventing and treating several skin diseases. Liposomes and nanoemulsions do not disturb the integrity of the

Table I Summary of commercially available delivery systems

Name Supplier Application

Natipide II Liposome Ultrasome Photosome Catezomes Elespher Microsponge Elesponge LipoCD-SA Unispheres Orgasol

Rhone-Poulenc Applied Genetics Applied Genetics Collaborative Labs Laboratories Serobiologiques Advanced Polymer System Laboratories Serobiologiques Lipo chemicals Induchem Elf Atochem

Reinforces skins own moisture retention capabilities Sun-care products Sun-care products Versatile active delivery Natural, botanical vehicle; pleasing visual effect High payload; improves cosmetic elegance of liquid Entraps a wide range of actives whilst softening skin Able to deliver oils in powder form Less sensitive to pH and surfactants; pleasing visual effect Improves skin feel and adhesion, offers controlled delivery and protection to variety of hydrophilic, lipophilic substances

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skin lipid bilayers and are not washed out while cleansing the skin. So, these formulations are believed to have a great future in the cosmetic science. The evolution of cosmetic patches is something expected after the warm acceptance of new cosmetic delivery systems by the consumers. Nonpassive cosmetic patches like, iontophoretic ones will nd in future several applications for more sophisticated cosmetic actives and ingredients. Patches of potent ingredients or extracts are expected to have a wide acceptance to achieve a very fast and effective action. Microsponges and microemulsions are also gaining good market value. Acceptability of microemulsions, however, would be governed by the use of safer surfactants, which do not appreciably change the permeability of membrane over repeated use. As research and development costs are on the rise, efcacy and safety are essential to assure a products sustainability in the market and repetitive purchases. This has created increased interest in delivery systems. In fact, the U.S. market for delivery systems has increased from $19 billion in 2000 to more than $41 billion projected for the year 2007. Some of the commercially available novel cosmetic delivery systems are summarized in Table I. Summary Novel cosmetic delivery systems reviewed here possess the potential to develop as the new generation smarter carrier systems after the liposomes. The technical, economic and sensory aspects should be taken into consideration while selecting an appropriate type of delivery system to enhance the safety, stability, extended efcacy and to enhance the aesthetic appeal of the nal product. However, despite the fact that the use of discussed delivery carriers for topical administration is very promising and highly attractive application area, further basic research needs to be carried out for a better understanding of the reasons for lipid modications, the effect of surfactants used for these modications and their transition during storage. Also, a better understanding is needed of how such systems modify the diffusion of actives into the skin, how lipid particles interact with the lipids of the stratum corneum and then how they affect penetration. Denitely, more human studies need to be carried out to have a real life data. After all, a delivery system is effective only, if it appeals to a consumer who is willing to use it and
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is founded on the no skin care without bioactivity principle. Acknowledgements The authors of this manuscript would like to express their thanks to the Institute of Chemical Technology for extending technical support during the preparation of this manuscript. In addition, the authors are thankful to Charbhuja Trading & Agencies, India, and Kamani Oil Industries, India, for their discussions during the compilation of this article and also to Sunder Medical Agencies, India, for their nancial support. References
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