Nanodermatolgy & Nanocosmetics

VISHNU AMBAREESH M S2007 BATCH

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Types of nanomaterials

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Liposomes

Liposomes are concentric bilayered vesicles in which the aqueous volume is entirely enclosed by a lipid bilayer composed of natural or synthetic phospholipids which are GRAS (generally regarded as safe) products. The lipid bilayer of liposomes can fuse with other bilayers such as the cell membrane, which promotes release of its contents, making them useful for cosmetic delivery applications. Their ease of preparation, enhanced absorption of active ingredients by skin and continuous supply of agents into the cells over a sustained period of time make them suitable for cosmetic applications. Vesicles, other than liposomes are being used these days that

claim to further enhance the penetration of substances across the skin, such as transferosomes, niosomes, and ethosomes.

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Nanoemulsions

• They are dispersions of nanoscale droplets of one liquid within another.They are metastable systems whose structure can be manipulated based on the method of preparation. The components used for their preparation are GRAS products and are safe to use. Their smaller particle size provide higher stability and better suitability to carry active ingredients; they also increase the shelf life of the product.

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• Milk (nanoemulsion)   © Unilever

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Nanocapsules

• Nanocapsules are submicroscopic particles that are made of a polymeric capsule surrounding an aqueous or oily core. It has been found that the use of nanocapsules decreases the penetration of UV filter octyl methoxycinnamate in pig skin when compared with conventional emulsions.

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• Nano titanium dioxide cluster (nanopigment)© L'Oréal Recherche

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Solid lipid nanoparticles

• They are oily droplets of lipids which are solid at body temperature and stabilized by surfactants.

• They can protect the encapsulated ingredients from degradation, used for the controlled delivery of cosmetic agents over a prolonged period of time and have been found to improve the penetration of active compounds into the stratum corneum.

• In vivo studies have shown to be more efficient in skin hydration than a placebo.

• UV-resistant properties, which were enhanced when a molecular sunscreen was incorporated and tested. Enhanced UV blocking by 3,4,5-trimethoxybenzoylchitin (a good UV absorber) was seen when incorporated into SLNs.

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Nanocrystals

• They are aggregates comprising several hundred to tens of thousands of atoms that combine into a “cluster”. Typical sizes of these aggregates are between 10 and 400 nm and they exhibit physical and chemical properties somewhere between that of bulk solids and molecules.

• They allow safe and effective passage through skin.

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Carbon nanotubes

• are stable carbon nanoparticles with potential anti-oxidant ability and cytoprotective effect.

• They have extremely small mean diameters (<100 nm). Their large inner volume allows the loading of small biomolecules while their outer surface can be chemically modified to render themselves various novel features that can be used to load proteins and genes for effective drug delivery.

• The conductivity of carbon nanotubes can be used to make highly sensitive sub-organellar biomarker sensor, thus, making the diagnosis of chronic skin infections and malignancies possible at an early stage

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Nanosilver and Nanogold

• Cosmetic manufacturers are harnessing the enhanced antibacterial properties of nanosilver(Silver is effective against Methicillin Resistant Staphylococcous aureus, onchomycosis, trichophtyon and dermal leishmaniasis, to name a few in a range of applications. Some manufacturers are already producing underarm deodorants with claims that the silver in the product will provide up to 24-hour antibacterial protection.

• Nano-sized gold, like nanosilver, is claimed to be highly effective in disinfecting the bacteria in the mouth and has also been added to toothpaste.

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Dendrimers• Dendrimers are unimolecular, monodisperse,

micellar nanostructures, around 20 nm in size, with a well-defined, regularly branched symmetrical structure and a high density of functional end groups at their periphery.

• They contain large number of external groups suitable for multifunctionalization.

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Cubosomes• Cubosomes are discrete, sub-micron, nanostructured

particles of bi-continuous cubic liquid crystalline phase. It is formed by the self assembly of liquid crystalline particles of certain surfactants when mixed with water and a microstructure at a certain ratio.

• Cubosomes offer a large surface area, low viscosity and can exist at almost any dilution level. They have high heat stability and are capable of carrying hydrophilic and hydrophobic molecules.Combined with the low cost of the raw materials and the potential for controlled release through functionalization, they are an attractive choice for cosmetic applications as well as for drug delivery.

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• However, at present cubosomes do not offer controlled release on their own. They have also been modified using proteins. A number of companies including L’Oréal, Nivia and Procter and Gamble are investigating cubosomes for cosmetic applications. Despite this interest, cubosomes have not yet led to products.

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Hydrogels• They are 3D hydrophilic polymer networks

that swell in water or biological fluids without dissolving as a result of chemical or physical cross-links.

• They can predict future changes and change their property accordingly to prevent the damage.

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Buckyballs

• Buckminster fullerene, C60, is perhaps the most iconic nanomaterial and is approximately 1 nm in diameter.

• It has found its way into some very expensive face creams. The motivation is to capitalize on its capacity to behave as a potent scavenger of free radicals.

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• Although fullerenes are hydrophobic, they can be organically functionalized by attaching hydrophilic moiety and become water-soluble and capable of carrying genes, proteins and other biomolecules for delivery purposes.

• Their small size, spherical shape, and hollow interior all provide therapeutic opportunities.

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•These have been proposed as rejuvenating cosmetic products like sunscreens, moisturizers, long lasting makeup, etc., Slow release kinetics are important in perfumes, which can yield all day fragrance. [10] Regardless of the desired application (transdermal or topical), the transport characteristics of the nanocarriers are related to its dimensions (hydrodynamic diameter and shape-spherical, elliptical, nail-shaped) and the pathway (via the intercellular route or the hair follicle).

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Picoparticles

• Picoparticles are approximately 2 to 3 orders of magni- tude smaller than that of nanoparticles and appear to be on an atomic or small-molecule scale. An example of a picoparticle would be water or an atom of zinc or titanium.

• one manufacturer, BIoNoVA, Inc, for Barneys New York has developed several proprietary nanotechnologies, which can be used as a technological platform for creation of multiple products oriented toward enhancement of self- healing processes. This technological platform is based on development of nanotechnology of bioactive complex modeling, which has the ability to manipulate not only with nano, but also with pico size particles.

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NOVEL CARRIERS FOR COSMETICS AND DERMATOLOGICAL

PREPARATIONS

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Microsponge

• It is a distinctive technology which utilizes microporous beads (10- 25 microns in diameter) for the controlled release of topical agents

• loaded with active agent having properties like inertness with monomer, adequate stability in contact with polymerization catalyst and process, immiscibility or slight solubility in water.

• Microsponge delivery system (MDS) release of active drug is carried out in a timely manner and also in response to other stimuli like rubbing, temperature, pH, moisture etc, onto the skin. MDS is being used in cosmetics, over-the counter (OTC) skin care, sunscreens and prescription products .

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• Commonly used drugs for microsponge delivery system are flubriprofen, benzylperoxide, fluocinolone acetonide, retinol etc.

• A microsponge formulation provides extended release with reduced irritation and improved patient compliance. These are stable and are self sterilizing capacity as particles are very small (0.25µm) size where bacteria cannot penetrate.

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• In cosmetic and dermal preparation wide variety of applications like in sunscreens for long lasting product efficiency and with improved safeguard for better protection from sunburns and sun related injuries even at high concentration and with decreased irritancy and sensitization,

• in antipruritics for long- lasting and enhanced activity,

• In rubefacients for prolonged activity with decreased irritancy Greasiness and odour,

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• , In skin depigmenting agents e.g. hydroquinone for enhanced stabilization against oxidation with better efficacy and aesthetic appeal,

• In antifungals for continuous release of active drug moiety,

• In antidandruff preparations like zinc pyrithione, selenium sulphide it is used to decrease obnoxious odour and also to minimise irritation and increase level of safety and effectiveness for long duration

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• In anti- acne preparations e.g. Benzoyl peroxide to maintained efficiency with reduced skin irritation and sensitization,

• in anti-inflammatory preparations e.g. hydrocortisone for longer duration of activity with decreased skin allergic response and dermatoses,

• Microsponge drug delivery system can also be used in Line Eliminator Dual Retinol Facia treatment-In this immediate and time released action of vitamin A is obtained by fading the appearance of fine lines, wrinkles and skin discolorations coupled with aging

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Following are the some marketed products of Microsponge drug delivery system with advantages • Aramis fragrances- High Performance Antiperspirant Spray for 24 Hours release of fragrance. • Carac Cream – It is prescribed as a single dose/day for the treatment of actinic keratosis (AK). • EpiQuin Micro- This is a prescription moisturizing fading cream that decreases effects of conditions like melasma, post inflammatory hyper pigmentation or solar lentigines and also helps in Age spots, Sun spots, and Facial discoloration. • Retin- for topical treatment of acne vulgaris. • Retinol cream, Retinol 15 Night cream-A night time treatment cream, continued use of Retinol 15 will help to reduce fine lines and wrinkles, and prominent improvement in the skin discolorations occur due to aging, and enhanced skin smoothness.

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• Sports creams RS and XS - Topical analgesic-anti-inflammatory and counterirritant used for managing musculoskeletal conditions.

• Micro Peel Plus/Acne Peel- These microcrystals target the correct areas on the skin that need improvement. • Oil Control Lotion- Day cream used to give matte finish and eliminates shine for hours after application. It soothes inflammation and leaves tighten skin and thus promote healing of acne-Prone oily skin conditions. • Lactrex™ 12% Moisturizing Cream- helps to moisturize dry, flaky, cracked skin.

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Vitamin and gold loaded nanofibre facial mask

• Conventional beauty face masks existing in the market are cotton masks that are pre-moistened with skin nutrients. The aqueous phase of the pre-moistened mask can raise the degradation rate of the unstable ingredients such as ascorbic acid.

• To overcome this problem a novel polymeric face mask have been developed that can accommodate several skin nutrients such as ascorbic acid, retinoic acid, gold, and collagen.

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• Many marketing tactics include the inclusion of antioxidants and other skin nutrients into cosmetic products.

• The strength and function of the skin depends upon an important factor i.e. Collagen which also play an important role in skin rejuvenation and wrinkle reversal effect. The quantity of collagen in the skin decreases along with age; therefore, it is extensively used as a moisturizer in cosmetic creams and products.

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• Generally Vitamin C (L-ascorbic acid) has been used in cosmetic and dermatological preparations for its photoprotective action, ability to destroy free radicals and oxidizing agents. It can also encourage collagen synthesis and suppress the pigmentation of the skin. Vitamin C is chemically unstable, and can be oxidized very easily; therefore, more stable derivatives (with ability to convert into active compound i.e. ascorbic acid after ingestion) like ascorbyl palmitate, ascorbyl tetraisopalmitate, and magnesium ascorbyl phosphate formulated as a emulsion are extensively used in pharmaceutical industry

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• Retinoic acid can be used in treatment of acne and also promotes the repair of skin damaged by ultraviolet and can decrease wrinkles caused by photoaging

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• Gold nanoparticles have been studied as potential vaccine carriers and in transdermal delivery.

• Nowadays Gold facial masks are being used in beauty clinics and saloons. It works by improving the blood circulation, skin elasticity, and thereby revitalizes the skin and also reduces the formation of wrinkles. Skin permeation studies demonstrate that spherical gold nanoparticles are not inherently toxic to human skin cell

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Applications…

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Two main uses for nanoparticles in cosmetic products are UV filtering

and delivery of active ingredients.

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SUNSCREENS

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• Recent sunscreens contain insoluble nanoparticles (colourless) of titanium dioxide (TiO 2) or zinc oxide (ZnO), which reflect/disperse ultraviolet more effectively than bigger particles.

• The nano-sized particles are used in sunscreens as a substitute to existing chemical UV absorbers, such as p-aminobenzoic acid and benzophenones, which can cause sensitivity reactions individuals

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• one common ingredient in broad-spectrum sunscreens, which protect the skin from both UVA and UVB rays, is avobenzone, which can make a sunscreen greasy and very noticeable when applied to the skin. Since titanium, another common sunscreen ingredient, requires an oily mixture to dissolve, a white residue can be apparent on the skin upon application. However, when these active ingredients in sunscreens are converted into nanoparticles, they can be suspended in less greasy formulations – which seem to vanish on the skin and do not leave a residue – while retaining their ability to block UVA and UVB light. 

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• nanoparticles shrink in size, they interact with light differently. If they are smaller than the wavelength of visible light, they may become transparent. Smaller nanoparticles also coat the skin more tightly and evenly than their counterparts. Microparticle (left); nanoparticle (right) 1/1000 size of microparticle (not to scale

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• Sunscreen that uses nanoparticles generated by ivy plants.  Research has shown that these ivy nanoparticles are more effective than oxide nanoparticles in blocking ultraviolet rays

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Titanium dioxide is the largest industrial produced nanoparticle in the

world, with typical industrial production down to 25 nm

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• Nano titanium dioxide clumps from a sun cream on the skin surface © L'Oréal Recherche

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anti-aging products

• When properly engineered, nanomaterials may be able to topically deliver retinoids, antioxidants and drugs such as botulinum toxin or growth factors for rejuvenation of the skin in the future.

• vitamin C is an antioxidant that helps fight age-related skin damage which works best below the top layer of skin. In bulk form, vitamin C is not very stable and is difficult to penetrate the skin. However, in future formulations, nanotechnology may increase the stability of vitamin C and enhance its ability to penetrate the skin. 

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• Topical paralytic agents, such as ã-aminobutyric acid, are being used to transcutaneously relax muscles of facial expression.

• Botulinum toxin has been stabilized and encapsulated in a form that allows penetration of the skin and apparent effacement of rhytides in early clinical trials

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• nanoparticles of hyaluronic acid can penetrate the skin making possible its topical application without the need of an injection

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• Some biologically active materials may be too large (botulinum toxin, hyaluronic acid) or polar (γ-aminobutyric acid) to penetrate the epidermis and may require injections for administration (left). Nanoencapsulated versions of these molecules may be stable and penetrate to the dermis (right)

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Diagnosis of cutaneous malignancies

Quantum dots, a type of nanoparticles, tagged with antibodies can be used for real time visualization of sentinel lymph nodes and cutaneous tumors, especially metastatic melanoma

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Lymph-node Mapping

• Sentinel lymph-node mapping is now a mainstay for surgery of intermediate-thickness and thick melanomas.

• It may soon be used for other types of invasive skin cancer such as squamous cell carcinoma.

• Tracers required for sentinel-node mapping must be optimized for hydrodynamic diameter, surface, charge, and contrast. Diameters less than 10nm can overshoot the draining lymph node. This results in the sentinel node being missed and multiple downstream nodes and possibly nodal basins being labeled. Molecules that are larger (50–100nm) either do not enter lymphatics or travel so slowly that 24 hours or more may be required for label uptake. Molecules with a negative surface charge enter lymphatics more readily and are retained in the lymph nodes better.

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• Recently, quantum dots have proved useful in identifying sentinel nodes using infrared fluorescence.

• allow for excellent realtime visualization of dye travel during a sentinel-node-mapping procedure. They also move rapidly due to their specific size of 15–20nm and are firmly anchored to lymph nodes with their anionic surface charge.

• they allow for non- radioactive detection.• Once optimized, they may prove superior to

other tracers for sentinel-node mapping.

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Future Melanoma Treatment

• gold when turned into a nanomaterial called nanoshells, has been shown to be a useful treatment for melanoma in animal studies

•  In one animal study done at MD Anderson Cancer Center in Houston, investigators joined gold nanoshells with a molecule which homes to melanoma. When these gold nanoshells are injected into mice harboring melanoma, the nanoshells accumulate in the cancerous tissue. When mice are illuminated with the proper wavelength of light, their tumors, laden with gold nanoshells, heat up and are effectively killed. The surrounding tissue, which lacks targeted gold nanoshells, is unharmed. 

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Nanomechanical and Nanotribological study of hair• used to study the mechanical characteristics of

hair. Understanding the differences between hair types allows cosmetic companies to create products to suit individual hair types (e.g. ethnic differences between Caucasian, Asian and African hair) as these can respond differently to activities like shampooing, styling or colouring.

• The hair care industry is also interested in the effect of water on the nanomechanical properties of hair.

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• Bhusan et al. have conducted nanoscratch tests, using Nano Intender II (MTS Nanosystems), to understand properties of different types of hairs at the nanoscale63. The studies demonstrated the difference in scratch resistance of single hair fibres of different ethnic regions as well as the coefficient of friction of hairs. They found that the first 200nm of the hair surface, irrespective of origin, is softer than the underlying layer. A further study into the hair fatigue due to stress and tension using AFM has shown that the ethnic hairs vary in mechanical properties

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Diagnosis of skin infections

• Carbon nanotubes’ can be linked to bigger molecules like nucleic acids and antibodies which in turn can bind their receptors. The electrical conductivity is different for isolated, coupled and receptor-bound coupled carbon nanotubes. Based on this unique property, a highly sensitive biomarker sensor can be developed for the real time diagnosis of cutaneous infections and may be malignancies.

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Treatment of skin infections

• Nanoparticulate chitosan has been used to encapsulate various volatile antimicrobial gases e.g. nitric oxide which is released when the polymer dissolves. It is utilized in treating cutaneous infections and abcesses.

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Treatment of spongiotic dermatoses

• Nanoencapsulated topical steroids absorb in the epidermis without penetrating the dermis. Therefore, help avoiding steroid side effects such as atrophy and telangiectasias and used in the treatment of spongiotic skin disorder

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Atopic Dermatitis

• filaggrin gene (FLG) is critical to the development of atopic eczema and ichthyosis vulgaris. In Caucasians, mutations R501X and 2284deI4 are present in at least 7–10% of the population. Improved barrier creams are being developed using nanotechnology. One of the most helpful would be a cream that would either deliver filaggrin itself to the skin or stimulate the synthesis of filaggrin. Furthermore, the cream could be formulated to deliver filaggrin to regions where transepidermal water loss is highest.

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Lamellar Ichthyosis

• Traupe et al. are working on a therapy for lamellar ichthyosis. The defect for one variant has been localized to transglutaminase.

• Traupe’s group has isolated and purified transglutaminase-1 and tagged it with six histidines for purification. They plan to package recombinant transglutaminase in cationic liposomes and make a cream for therapy.

• The project is supported by a Foundation for Ichthyosis and Related Skin Types grant. If successful, enzyme-replacement therapies may be modified for other cutaneous genetic diseases.

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Sebaceous gland targeting

• targeting strategies for hair follicle related disease like acne, rosacea get benefit from the follicular penetration of topically applied particles like poly(lactic-co-glycolic) acid, biodegradable poly-lactic acid, solid lipid nanoparticles and liposomes loaded with active drug moiety.

• A major advantage is the better tolerability of irritating retinoid improving patient compliance as well as the avoidance of systemic absorption and side effects.

• The extensive research in recent years has led to the commercialization of certain particle-based anti-acne products of benzoyl peroxide (BP, such as a BP microsphere cream 5.5% (NeoBenz Micro(R), SkinMedica, Inc.) and a BP microsphere wash 7% (NeoBenz Micro Wash Plus Pack(R), SkinMedica, Inc.).

• Clinical studies showed high levels of skin tolerability, esthetic attributes and patient satisfaction after treatment with BP-loaded microsphere creams

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Laser ablation and phototherapy

• Short laser pulses already have been used in ophthalmology and dermatology to target melanosomes and thus treat hyper- pigmentation disorders of the skin or retinal disorders.

• Examples of nanoparticles used are iron oxide, gold.

• Photodynamic therapy (PDT) by using gold nanoparticles have been seen as a promising treatment strategy of skin cancer and various skin diseases, but its use has been limited due to the costs and patient compliance (pain)

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Treatment of hair diseases

• treatment of hair disorders like alopecia androgenetica and alopecia areata.

• by increasing drug penetration into the hair follicle openings and can act as a depot for a sustained drug release within the hair follicle. Examples of nanoparticles used to treat hair disease are poly(lactic- co-glycolic) acid, poly (e-caprolactone)-blockpolyethylene glycol, neutral liposomes, solid lipid nanoparticles

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• Encapsulated topical steroids are being developed, which accumulate in the epidermis, but do not penetrate the dermis, where collagenolysis associated with atrophy and telagiectases occurs. These types of agents will be useful for the management of spongiotic dermatoses and will carry a reduced risk of corticosteroid-mediated side-effects.Bulk soybean oil is not toxic. Nanoemulsions of soybean oil are antimicrobial and are being incorporated into disinfectants. Nanoemulsions of other compounds that can penetrate the nail and the pilosebaceous unit are being used to treat onychomycosis and acne, respectively.

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Topical dermatotherapy

• use would prove beneficial for local treatment of inflammatory skin diseases as well.

• Glucocorticoids are key drugs in dermatology, but with side effects like skin atrophy which limits their chronic use. It has recently been shown that a targeting of the epidermis, where the inflammatory process takes place, instead of the dermis, can be achieved by using liposomal formulations, thus minimizing skin atrophy.

• Several other studies indicate that various drugs such as podophyllotoxin, cyclosporine A, tacrolimus methotrexate, psoralen, dithranol, clotrimazole and other antifungal drugs could be integrated in nanoparticles to achieve a better tolerability, an increased safety and an optimal therapeutic effect

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Thermosensitive nanoparticle polymers

• Thermo-sensitive polymers encapsulate drugs below a critical temperature and dissolve to release the drug above the critical temperature.

• These are being used for drug delivery at the sites of inflammation or wherever external heat is applied. This is the basis of treatment of localized psoriasis (especially nails and scalp) using methotrexate encapsulated in a thermosensitive polymer.

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Gene therapy • As previously mentioned, the hair follicle and

more specifically the bulge region and the hair matrix accommodate a substantial population of stem cells.

• Since nanoparticles can penetrate selectively into the hair follicle canal, nanoparticulate formulations could be used for gene delivery, creating new potential in the emerging field of gene therapy.

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• Polymeric nanoparticles encapsulating small inhibitor ribonucleic acids (siRNAs) can selectively inactivate gene expression.

• Nanoencapsulated siRNAs have been used for the management of a genodermatosis (pachyonychia congenital) and for the successful targeted delivery and inhibition of a test gene expressed in melanoma in human trials.

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Transdermal drug delivery

• Several opiates are already commercially available as a patch. Unfortunately, the strong lipophilic stratum corneum hinders the permeation of hydrophilic molecules and retains high lipophilic drugs, thus limiting the transdermal delivery of strong lipophilic or hydrophilic molecules.

• Hair follicles could play an important role as a shunt for the systemic absorption of topically applied drugs.

• Recently nanoparticles have been used as a drug carrier for transdermal drug delivery system.

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• encapsulation of substances in nanoparticles enhances their transdermal penetration and permeation as a result of the follicular targeting.

• The nanoparticles used are calcium carbonate, solid lipid nanoparticle, nanostructured lipid carrier. More recently, polymeric nanoparticles and electroporation were successfully used for the transdermal delivery of insulin to overcome drawbacks of subcutaneous drug administration like patient discomfort, localised drug reaction e.g., lipoatrophy and granuloma formation etc

• transdermal drug delivery could modernize treatment strategies for Diabetes and chronic pain by offering much more patient compliance

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Gene analysis• . Dr. James T. Elder, from the University of Michigan, discussed

how gene chips make it possible to identify infrequent or low risk alleles for psoriasis. It is now possible to test cohorts of up to 30,000 patients and thus obtain the statistical strength to identify these previously elusive alleles.

• Dr. Costanzo uses nanotechnology in the form of next generation sequencing technology coupled with chromatin immunoprecipitation (Nano-ChIP-seq) to explore the pathogenesis of psoriasis.Using Nano-ChIP-seq, Dr. Costanzo and his colleagues have shown that IKKα is downregulated in patients with psoriasis, and they have discovered a novel nuclear function of IKKα as a repressor of inflammatory genes in keratinocytes.

• Both of these researchers highlighted how they capitalize on both the cost saving and data enhancing benefits nanotechnology confers to gene chips.

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treatment of chronic itch• Futuristic• if there is a reservoir of nanoparticles that collect along

the hair follicle it would hold enormous potential for the treatment of chronic itch.

• nerve fibers in the epidermis and epidermal-dermal junction (DEJ) are overactive in patients with chronic itch, and the hair follicle is an important target for anti-itch medication.

• The development of ultra-small polymer particles that allow for the controlled release of anti-pruritics would enable targeted drug therapy focused on the epidermis, DEJ skin and nerve fibersmany potential targets along the hair follicle, from the infundibulum (CB1, CB2, and NK1) to the hair bulb (CB2, TRPV1, NK1, B-endorphin) and dermal papilla (SP, CGRP, MOR).

• Sensitization to itch is associated with nerve growth factors, including G-protein coupled receptors, and ion channel receptors.

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• The stratum corneum is in close proximity to fibers containing these receptors., "If you remove the upper layers of skin, you don't have itch, you only have pain." Because topical nano-therapeutics concentrate in the upper layers of the skin, nanotechnology offers potential for the treatment of itch. Future perspectives of nanodermatology therapies for itch include the development of ultra-small polymers that allow controlled release of anti-pruritics, as well as combination drugs that make possible precise feedback mechanisms that can safely regulate the release of drugs on board na-noparticles to maximize activity, while minimizing toxicity.

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Immunomodulation and Vaccine Delivery via Skin

• . Skin is the main route to allergen sensitization .Langerhans cells (LCs) and dermal dendritic cells are two types of skin-resident antigen-presenting cells that express CD1a, a protein that mediates antigen presentation.T cells are also abundantly present in normal skin .

• The possibility to exploit nanotechnology to modulate the immune system and to deliver vaccines through skin are active research area of increasing importance as recently reviewed

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Antimicrobials and Wound

Healing

• Silver ions have long been used for their inherent antimicrobial properties .Silver ions are thought to inhibit bacterial enzymes and bind to DNA , whereas nano Ag is reported to induce bacterial cell wall and cytoplasmic membrane damage .

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• Literature also supports the antimicrobial activity of nitric oxide (NO) and its use to promote wound healing

• nitric oxide–releasing nanoparticles (10 nm) made from tetramethylorthosilicate, polyethylene glycol, and chitosan.

• Nitric oxide gas was trapped in the hydrogel/glass composite matrix and released upon contact with water. Topical application of these nanoparticles was reported in this journal to be highly effective against cutaneous methicillin-resistant Staphylococcus aureus infection in a mouse model

• may be ideal for applications in combat or disaster situations where emergency personnel could apply them directly to trauma wounds in the field.

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• Other examples are Chlorhexidin-loaded nanoparticles (Nanochlorex), uncoated TiO2 possess antibacterial properties due to their photocatalytic action.

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Color Control

• Human skin is largely translucent. • Three aspects of skin beauty are color correction,

gloss correction, and face-shape correction. • Color comes from a combination of skin type and

ambient light impinging on the skin. Only about 5% of surface light is reflected; the remainder penetrates the skin, where it is scattered and absorbed. Melanin and hemoglobin absorb almost half of the light, and the other half eventually makes its way out of the skin. Melanin absorbs UV light, hemoglobin absorbs mid-wavelength yellow and green light, and the exiting light is red or infrared. The pattern of this light gives the skin its appearance and beauty.

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• Nanometer-thick titanium-coating mica powders can alter this pattern. Titanium-coated mica powders in foundation are superb at color correction, but give the skin too much gloss.

• When incorporated with composites of nanoscale barium chloride and sodium sulfate, this gloss gives way to a matte-like finish. If the surface coatings are larger (1,000–1,500nm), they scatter light. If 20–50% of the nano-sized titanium mica are coated in this way, they reflect light in the mid-face and scatter light on the periphery of the face. This causes facial contrast, making the face look more 3D and causing face-shape correction. These scattering properties can be modified by altering the shape of the particles themselves from plate-like to spherical to needle-like

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• . Further modifications may be able to enhance internal reflection of light at the skin–air interface or alter the wavelength of outgoing light to create a glow. This could be used for color correction or for apparent surface correction of fine lines, blemishes, or shadows. Furthermore, variation of the size of particles is being used to create make-up colors of nearly infinite as well as iridescent hues, such as those on the wings of a butterfly.

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Supercloths???• Fabrics incorporating superhydrophobic

'nanowhiskers' (nanosized hair-like projections on individual textile fibers) can repel stains, dirt, and microorganisms.

• Fabrics impregnated with nanosilver are antimicrobial and may be beneficial to health care workers.

• Nanosilver is also being incorporated into dressings or bandages to minimize the potential for wound infection.

• Nanosilver in washing machines allows disinfection at lower temperatures and saves energy

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• Fibers can be specifically designed to be bacteriostatic or fungistatic, to absorb fluids, to be breathable, to be hemostatic or non-allergenic, and to incorporate growth factors or medications. They may contain natural materials such as alginate, chitin, and collagen. They may contain carbon fibers or be made of composite materials that are woven, non-woven, knitted, crocheted, braided, or pressed.

• may have additives that relieve pain, reduce odor, or provide cushioning or breathability. They may provide compression that is fixed, variable, or graduated. Fibers can already be made from yarns of cotton, silk, polyester, nylon, or wool and coated with nanomaterials. These fibers, if coated with nanosilver 10nm in size and 0.4–0.9% in weight, are effective against most bacteria, fungi, and viruses.

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• Smart Clothing One company- conductive fiber grid integrated into the shirt and is washable. When the shirt is connected to sensors that detect electrical activity and also stretch, the shirt can be used to monitor its wearers.

• For example, athletes and patients can use the shirt to monitor heart rate and respiration. Other potential sensors could detect sweat rate and body temperature. This information could be relayed wirelessly to local or distant receivers

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Indian cricket team???

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• Researchers have also created nanobatteries that can generate electricity from the movement and rustling of fabric.

• In the future these integrated kinetically charged batteries could allow a shirt, or any item of fabric, to generate power.

• to monitor UV light exposure in patients who are sun-sensitive or to monitor body temperature in patients who have hypohidrotic disorders.

• could also detect excess sweat and locally release antiperspirant or detect warmth from itch and locally release anti-inflammatory medication.

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nanopunch• a small, simple biopsy tool consisting of copper,

nickel, silicon, and chromium layered in the shape of an origami claw.

• Differing coefficients of expansion of the layers allow temperature change to cause the claw to close and open, like a Venus flytrap.

• The nanopunch is paramagnetic and its migration can be controlled by a magnetic field.

• The nanopunch could be injected into the bloodstream and guided to challenging biopsy sites, such as the nail matrix, the fascia, and the liver.

• The claw could be activated by temperature and collected from a urine sample by a magnetic trap. Tissue could then be released for analysis.

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Nanosized metals

• first described by Michael Faraday in 1857. • include selenium, copper, zinc, magnesium, and iron. • Selenium is an important antioxidant for the skin, and

protects the skin through involvement with glutathione peroxidase and thioredoxin reductase. Selenium sulfide is used in rinse of products such as dandruff shampoos.

• Copper is commonly found in wound healing and anti-aging products, and possesses antimicrobial and antiviral activities. Copper containing pillowcases have been found to reduce wrinkling by stimulating extracellular matrix protein production.

• 11% of the zinc in the body resides in the epidermis, and zinc compounds are used in dandruff shampoos, antifungals, and sunscreens

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• Metal nanoparticles are used in both cosmetics and potential cosmeceuticals.

• The high surface area to volume ratio of nanoparticles creates an increased driving force for diffusion across the skin barrier.

• Their small size confers the benefit of invisibility, as these nanoparticles are 4-7 times smaller than the visible wavelength of light.

• These metal nanoparticle cosmeceuticals can potentially deliver metals necessary for wound healing and collagen remodeling to potential benefit.

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e-Skin • another, engineers at the University of California at

Berkeley recently developed a pressure-sensitive electronic material from semiconductor nanowires that functions like human skin.

• first such material made out of inorganic single crystalline semiconductors.

• It could some day restore the sense of touch to patients with prosthetic limbs. With major players like Merck, Schering-Plough and Johnson & Johnson providing funding, and major research institutions across the globe devoting time and effort to its study, what seemed like science fiction just a few years ago could well be the nanotechnology-based realities of tomorrow

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Health hazards!!!!!

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• Large number of risks both to humans as well as to the environment.

• The toxicity of nanomaterials is affected by their properties, which are attributable to their smaller size, chemical composition, surface structure, solubility, shape and aggregation.

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Smaller size of nanoparticles

• create the opportunity for increased uptake and interaction with the biological tissues

• production of reactive oxygen species, including free radicals which will result in oxidative stress, inflammation, and consequent damage to proteins, membranes and DNA.

• can easily gain access to the blood stream via skin or inhalation and from there they will be transported to the various organs. The high dose and long residence time of the nanoparticles in the vital organs can lead to their dysfunction

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Carbon nanotubes have been shown to cause the death of kidney cells and to inhibit further cell growth

Whereas 500 nm titanium dioxide particles have only a small ability to cause DNA strand breakage, 20 nm particles of titanium dioxide are capable of causing complete destruction of super-coiled DNA, even at low doses and in the absence of exposure to UV

Another study found that mice which were subacutely exposed to 2–5 nm TiO2 nanoparticles showed a significant but moderate inflammatory response

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Shape of nanoparticles

• Nanoparticles are produced in a variety of shapes like spheres, tubes, sheets etc. and this may be a major cause for the health risks caused by them. A study has shown that exposing the abdominal cavity of mice to long carbon nanotubes are linked with inflammation of the abdominal wall

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Surface area of nanoparticles

• As the size decreases, their surface area increases leading to an increase in their reactivity. Nanomaterials are also highly reactive due to their high surface area-to-mass ratio, providing more area by weight for chemical reactions to occur, because of which some nanoscale particles may be potentially explosive and/ or photoactive. E.g.anoscale titanium dioxide and silicon dioxide—may explode if finely dispersed in the air and they come into contact with a sufficiently strong ignition source

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Penetration of nanoparticles

via skin

• nanoparticles up to 1000 nm in size can penetrate skin, especially if skin is flexed or massaged.

• Broken skin is a direct route for the penetration of particles even up to a size of 7000 nm.

• The presence of acne, eczema and wounds may enhance the absorption of nanoparticles into the blood stream and may lead to further complications.

• penetration was deeper in skin affected by psoriasis than in unaffected skin.

• Recently, the base carriers are being modified in order to enhance the skin penetration by incorporating certain penetration enhancers, both physical and chemical, and also by preparing newer vesicular systems with increased skin penetrability like ethosomes and transferosomes

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Cellular toxicity - zinc oxide & titanium

dioxide

• In study by Minghong Wu and co-workers at Shanghai University, ZnO nanoparticles used in sunscreens can damage or kill the stem cells in the brains of mice.Wu et al. prepared cultures of mouse neural stem cells (NSCs), and treated them with zinc oxide nanoparticles ranging from 10 to 200 nanometers in size. After 24 hours, the cell viability assay indicated that ZnO nanoparticles manifested dose-dependent, but not size-dependent toxic effects on NSCs. Through analysis using confocal microscopy, transmission electron microscopy examination, and flow cytometry, many of the NSCs showed clear signs of apoptosis. This zinc oxide nanoparticle toxicity was found to be the effect of the dissolved zinc ions in the culture medium or inside cells.

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• In another work by Arnaud Magrez at the NN Research Group, it was found that titanium dioxide based nanofilaments were found to be cytotoxic, which was affected by their geometry and also enhanced by the presence of defects on the nanofilament surface, resulting from chemical treatment. Nanofilament internalization and alterations in cell morphology were observed

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Occupational risks of

nanoparticles

• Workers may be accidentally exposed to nanomaterials during the production of nanomaterials or products containing them, as well as during use, disposal or recycling of these products. Exposure may also occur in cleaning and maintaining research, production and handling facilities.A higher potency of nanomaterials compared to microsized particles was detected by Kaewamatawong et al. At present, there is insufficient information according to the European Agency for Safety and Health at Work. In addition, because nanomaterials have applications in many consumer products and the use of such materials in products is increasing, consumers have an increasing chance of exposure to these materials..

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Chronic exposure• most real world exposure to nanomaterials is

chronic. The potential for nanomaterials to gradually accumulate in tissue over a long period of time is the most concerning. He showed that Chinese Hamster Ovary cells (CHO) have a concentration dependent increase in ROS in both acute and chronic TiO2 exposed cells. Over time, the effect of TiO2 diminishes in chronically exposed cells. Overall, however, CHO cells appear to adapt to chronic exposure of nano TiO2 .the effect of TiO2 on cells seems to be minimal without light

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Route and extent of exposure

• health risks that nanoparticles pose to the humans also depend on the route and extent of exposure to such materials. Nanomaterials enter the body mainly through 3 routes

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Inhalation

• most common route of exposure of airborne nanoparticles according to the National Institute of Occupational Health and Safety. For eg. workers may inhale nanomaterials while producing them if the appropriate safety devices are not used, while consumers may inhale nanomaterials when using products containing nanomaterials, such as spray versions of sunscreens containing nanoscale titanium dioxide. According to officials at the National Institutes of Health, although the vast majority of inhaled particles enter the pulmonary tract, evidence from studies on laboratory animals suggest that some inhaled nanomaterials may travel via the nasal nerves to the brain and gain access to the blood, nervous system, and other organs, according to studies we reviewed.

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Ingestion

• Ingestion of nanomaterials may occur from unintentional hand-to-mouth transfer of nanomaterials or from the intentional ingestion of nanomaterials.

• A large fraction rapidly pass out of the body; however, according to some of the studies a small amount may be taken up by the body and then migrate into organs.

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Through skin• Studies have shown that certain nanomaterials

have penetrated layers of pig skin within 24 hours of exposure.

• According to some of the studies reviewed by the US Government Accountability Office (GAO), concerns have been raised that nanomaterials in sunscreens could penetrate damaged skin.

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Environmental risks of

nanoparticlesexposure of nanomaterials through release into the water, air, and soil, during the manufacture, use, or disposal of these materials, if antibacterial in nature and if released in sufficient amounts, could potentially interfere with beneficial bacteria in sewage and waste water treatment plants and could also contaminate water intended for reuse, according to some of the studies reviewed by US GAO. For example, studies have revealed the toxicity of TiO2 nanoparticles to the main body systems of rainbow trout.In a study conducted by the University of Toledo, the researchers discovered that nano-titanium dioxide used in personal care products reduced biological roles of bacteria after less than an hour of exposure. These findings suggest that these particles, which end up at municipal sewage treatment plants could eliminate microbes that play vital roles in ecosystems and help treat wastewater.

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• Rice University's Centre for Biological and Environmental Nanotechnology has pointed out the tendency for nanoparticles to bind to contaminating substances already pervasive in the environment like cadmium and petrochemicals. This tendency would make nanoparticles a potential mechanism for long range and widespread transport of pollutants in groundwater.

• An interdisciplinary team of researchers at the UC (University of California) Santa Barbara produced a groundbreaking observation on how nanoparticles are able to biomagnify in a simple microbial food chain.

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Toxicity produced by carbon fullerenes (buckyballs)

• Various studies have shown that carbon fullerenes, which are currently being used in moisturizers and some face creams, have the potential to cause brain damage in largemouth bass, a fish species accepted by regulatory agencies as a model for defining ecotoxicological effects, kill water fleas and have bactericidal properties.

• Fullerenes have even been found to be toxic to the vascular endothelial cells.

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Issues……...

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• The buzz around nanodermatology is growing thanks, in part, to President Obama. In his 2011 State of the Union address, the President “discussed recent research related to nanotechnology-based treatment for melanoma,”

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• Nanoparticles (NP's) are found throughout nature, during combustion reactions, in volcanic eruptions, erosion, and people are naturally exposed to NP's all the time. There is therefore a natural adaptation and tolerance to NP's that is imperative for survival

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• In July 2012, materials supplier Antaria came under fire from environmental groups for providing metal oxide powders containing nanoparticles for a number of sunscreen brands which were advertised as nanoparticle-free. This highlights the issue with classification of nano-enhanced products - the particle size distribution of many powders will include some nanoscale particles, and it is not clear how much this affects the health implications of nanomaterials.

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????• From available literature, the penetration of ZnO and

TiO2 nanoparticles pose minimal health concern.

• ZnO is soluble in acidic environments, and the acidity of the skin stratum corneum likely induces dissolution and penetration of ionic Zn. Zinc is an essential mineral and therefore poses minimal toxicity concern.

• TiO2 nanoparticles are highly insoluble and are prone to agglomeration, which may hinder their penetration. Furthermore, stability and low toxicity of TiO2 are two properties that have long been exploited in the successful use of Ti metal for dental and orthopedic implants

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• The adjuvant effect of these and other types of nanoparticles that may contact barrier-defective skin, as well as the effect of UVR induced immunosuppression on nanoparticle skin interactions, remain important open questions. Limited data exist on nanoparticle interaction with diseased skin. Atopic dermatitis and psoriasis are common conditions on the rise. Contact hypersensitivity is a common occupational disease. The effects of these barrier-altering skin conditions on the penetration and transport of nanoparticles are largely unknown

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Companies at large…..

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• “Certainly, some of the early leaders in nanodermatology have been the cosmetic companies,” says Adnan Nasir MD PhD, president of the Raleigh, North Carolina-based Nanodermatology Society (nanodermsociety.org). Now, the medical and device side of the research and development equation is catching on.

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• a substantial proportion of patents issued for nanotechnology-based discoveries are currently in the realm of cosmetic and consumer skin care products. In fact, the cosmetic industry leads all other industries in the number of patents for nanoparticles, which have the potential to enhance sunscreens, shampoos and conditioners, lipsticks, eye shadows, moisturizers, deodorants, after-shave products and perfumes

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Cosmetics giant L'Oréal invested $927 million in cosmetic and dermatological research in 2011 and is an industry leader in nanotechnology-related patents.

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Oro Gold Cosmetics, whose products cost as much as $1,398 for a face mask, includes gold nanoparticles in its formulas and claims that these nanoparticles have anti-inflammatory and antioxidant properties, drive tissue regeneration, restore skin elasticity, and reduce signs of stress and aging. However, there isn’t concrete proof that these tiny particles pack such a massive punch

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• Lifeline Skin Care has a line of products that they claim can rejuvenate skin cells.

• They use stem cells (the nonembryonic kind), which is a type of cell that has the capability to stimulate the rejuvenation of other cells. The stem cells produce proteins that direct cells to build new cells to repair damaged skin tissue. The company encapsulates the proteins in nanoparticles.

• When you spread the serum containing the nanoparticles on your skin, they open, delivering proteins directly to your skin.

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• Antaria uses nanoparticles of zinc oxide to make a sunscreen called ZinClear-IM. This sunscreen protects you from the UV without leaving behind a white coating

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• amerElite Solutions manufactures the collagenFusion Skin care Systemto reduce the appearance of fine lines and wrinkles, along with moisturizing and hydrating the skin.

• The active ingredient is a trade secret called collamin-G. The manufacturer states that its components are approxi- mately 200 to 500 times smaller than a pore of the skin; therefore, approximately 200 to 500 elements penetrate the skin through a single pore at one time.5 The product is used to reduce fine lines.

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• colorescience makes Dual Finish Pressed compacts, which use nanotechnology and vitamins incorporated in mica that deliver antioxidants to the skin.

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• One company, Nanobio (www.nanobio.com), offers a nanoemulsion product derived from soybean oil with indications including the treatment of herpes labialis and onychomycosis, and vaccine delivery.

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• The nanoemulsion formulation of la Prairie Skin caviar ampoules, available at Bergdorf Goodman, permits maximum penetration of the exclusive, pat- ented cellular complex.

• It is available as 2 separate ampoules: a powder containing pure vitamin c, which is mixed with the nanoemulsion.

• The complex is reported to brighten the skin and eliminate fine lines.

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• Some manufacturers rely on a network or polymer to drape over the skin, coat it, and protect it, and to serve as a reservoir of long-lasting, time-released anti- aging compounds. one example is DiorSkin Forever Extreme Wear Flawless Makeup SPF 25, manufactured by Dior. The company makes a nanostretch network, which is “an invisible, micro-airy nano-network for a perfect complexion.”

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• lancôme advertised their rénergie series. Products included rénergie microlift Flash Lifting, which performs “25,000 microlifts for results in a flash,” and rénergie microlift Serum, which contains microlifters enhanced with a powerful tensing agent to immedi- ately tighten skin for an instant lifting effect that lasts all day. The microlifters are made of nanoparticles of silica and proteins that presumably form a dermo- bonding network to immediately lift, tighten, and firm the skin. These products have since been discontinued for unknown reasons.

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• L’Oréal has revitalift line. • A compatible Anti-Wrinkle 1 Firming Day cream

packages retinol and vitamin E into nanosomes to allow penetration of the skin’s surface. The revitalift anti-Wrinkle Firming Facial cloth mask is a cloth mask that contains nanosomes of proprietary Pro-retinol a and Par-Elastyl. These are designed to make skin firmer and fight against the signs of aging.According to the manufacturer, the mask is “infused with 7X your daily dosage of anti-wrinkle moisturizer, so you get a weeks’ worth of treatment in just 10 minutes.”

• Powerful deep delivery of product and speed of action

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• to enhance the skin’s appearance and protect the skin is DiorSnow Pure UV Base SPF 50, manufactured by Dior, which contains a makeup base and a brightener and delivers UVA and UVB protection.

• Diorskin Forever Extreme Wear Flawless Makeup SPF 25 also uses polymer technology and a nanostretch network, which the manufacturer states is “an invisible, micro-airy nano-network for a perfect complexion.”

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• JUVENA of Switzerland selected the absolutely best size for cosmetic skin care – 40 nanometers

• makes it possible to place the sensitive ingredients in the form of tiny crystals directly into the cell nucleus.

• The crystals fulfill two tasks at the same time: they are the active substance and a means of transportation—all in one—traveling deep and directly into the skin where they provide a ‘supply’ depot. From here the skin can take what it needs, whenever it needs it. The availability and accessibility of the substances for the cells is thereby increased and the protective mechanism optimal.

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• Bella˘Pellé manufactured an EGF complex cocktail that topically delivers antioxidants to the skin in Fullersome packages.

• This product has been discontinued.

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• Kara Vita manufactures Enlighten me! to correct skin discoloration and to even skin complexion. Nanospheres deliver active ingredients in a time-release formula to allow improvement of dyschromia in 2 to 8 weeks. The manufacturers recommend their Face Essential with SPF 15 moisturizer be used to prevent future discolor- ation. also for dyschromia,

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• KOSÉ corporation manu- factures rutína Pure White to enhance the appearance of chronic lentigines, which appear with minimal UV exposure. The product is designed to reduce pigmenta- tion.

• KOSÉ corporation also manufactures a compatible rutína Nano-Force Nourishing milk, a moisturizer that delivers a hyaluronic acid derivative

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• Fullerenes are employed by SIrcUIT cosmeceuticals in SIrcUIT White Out, SIrcUIT O.m.G. serum, and SIrcUIT Sircuit addict, and reportedly deliver a complex of skin nutrients designed for skin rejuvenation. The manufacturers note that fullerenes are more effective car- riers of active ingredients than liposomes and nanosomes and are 10 million times smaller. The company’s source is Shungite, which is an anthracite from the Shun’ga village in the Onega Lake area in the Karelia republic of russia, which has been reported to contain fullerenes.

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• Zelens makes a fullerene c-60 Day cream, c-60 Eye cream, c-60 Night cream, and a DNa Protection Day cream. The company touts the free radical scavenging properties of fullerenes and promotes the antioxidant properties of their products. one study has shown that a-alanine c-60 is comparable in its radical scavenging ability as thiourea and ascorbic acid.

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• Freedom Plus corporation makes Doctor Gunderson’s rãahj Nano copper Facial Spray as a rejuvenating application. I

• t has a companion product, Doctor Gunderson’s rãahj Synergized DhEa Facial Spray, whose active ingredient is dehydroepiandrosterone.

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• less traditional uses of topical skin care products include those which act to decrease fat and to augment breast tissue. at one point, Osmotics cosmeceuticals manufactured Lipoduction Body Perfecting complex.

• lipoduction contains high levels of pure grapeseed extract, an antioxidant proven to strengthen the capillary system and help pre- vent breakdown of the collagen matrix.

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• Stherb cosmetics International co, Ltd, makes Nano Breast cream, which is a “combination of Nanotechnology and the timeless Thai herb, Pueraria Mirifica.

• Nanosomes are oxidation stable compound which expands the cellular substructure and promotes development of the lobules and alveoli of the breasts company reports that subjects “can instantly experience Natural Breast Enlargement & Firmness.

• added advantage - Toning of Breast Skin, visible cleavage, radiant texture of breast skin & protection from free radicals.”

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• Treating Acne acnel makes a nanolotion for dry acne skin.

• Kara Vita makes clearly It! complexion mist, clearly It! Spot Treatment, and clearly It! acne Treatment Lotion, which have nanospheres containing sulfur, tea tree oil, and salicylic acid

• Ag NanoTech, Inc, makes Bye Bye Acne, a proprietary nanosilver delivery system. Bye Bye Acne is compliant with the US Food & Drug Administration monograph on acne over-the-counter drugs, sustainable ingredients, eco-friendly packaging, and manufacturing in the United States.

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Safety requisites for a blooming beauty

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• Cosmetic manufacturers using nanotechnology confront an uncertain future from both consumer response and a regulatory standpoint.

• Eminent scientific bodies like the Royal Society, Britain's most prestigious scientific body, and the US Food and Drug Administration warn that the health risks of nanocosmetics require a thorough investigation before product commercialization.

• One of the major problems is that there is not much evidence about how much or what type of safety assessments are done by the various cosmetic manufacturers on their products.

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• Though there are increasing number of cosmetics and personal care products containing nanomaterials in the market, there are no specific regulations regarding their safety assessment.

• In Australia, the National Industry Chemicals Notification and Assessment Scheme (NICNAS) regulates the safety of ingredients in cosmetics and personal care products and the Therapeutic Goods Administration (TGA) regulates sunscreens. However these regulators fail to distinguish between nanoparticles and larger sized particles.

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• The EU's Scientific Committee on Consumer Products (SCCP) looked at the safety evaluation of nanomaterials for use in cosmetic products and considered the implications on animal testing and whether the previous opinions on nanomaterials currently used in sunscreen products would need to be revised.

• The European Parliament approved the amended recast of the EU Cosmetics Directive, introducing the mention of ‘nanomaterials’ into an EU legislation. As requested by the European Parliament, the new regulation introduces a safety assessment procedure for all products containing nanomaterials, which could lead to a ban on a substance if there is a risk to human health.

Kindly give feedback…..

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When things are small never forget the big picture!!!!