Chitin Nanofibrils :An Innovative Cosmetic Delivery System

P. MorgantiProfessor of Applied Cosmetic Dermatology, II University of Naples

Visiting Professor of China Medical University ShenyangHead of R&D, Mavi Sud s.r.l

Mavi Sud s.r.l.Via dell’Industria 1,04011 Aprilia (LT)- Italy morganti@mavicosmetics.it

CHITIN NANOFIBRILS

BIOLOGICAL SIGNIFICANCEIn chemical terms chitin is a natural polysaccharide, present in scrub and shrimp shells formed by glucosamine and N-acetyl glucosamine, linked in a glycoside structure. (Muzzarelli RAA, et al., 1999; Muzzarelli R.A.A. and Muzzarelli C. 2005)Its alfa-nanocrystalline form separated by a patented process, is used as nanofibril of 240x5x7 nm in dimension. These nanocrystals, exhibiting an exceptionally high surface (up to 400 m2/gr), have demonstrated a relevant biological significance. Thus they are able to activate fibroblast proliferation and cytokine production, favoring the giant cell migration, macrophage activation and neovascolarization. Due to its molecular conformation and its particular chemical-physical activity, the chitin nanofibril (CN) is capable not only to establish ionic bond with a great quantity of water, just as yaluronic acid (YA), but also to form complexes with different active ingredients delivering them to different site of the skin for different periods of time, in depending of the selected vehicle used. (Morganti P. et al., 2007).

CHEMICAL ACTIVITYHaving CN the same backbone of YA, it is strongly hydrophobic and capable to attract and bind many molecules of water, establishing also stable ionic bonds with the negative sulfate location of the glycosaminoglycans (GAG). CN, in fact, is a polysaccharide strongly positively charged. can be selected to obtain a local or global activity at level of lipid bilayer membranes, or the extracellular matrix rich in GAGs. Therefore, the outmost layer of the stratum corneum (SC) (sunscreens), the whole SC or the intercorneocitary lipids (lipid lamellae) or the corneocytes themselves within the SC (moisturizing ingredients),the viable epidermis and the dermis (anti-aging and antioxidant compounds), but also structural entities such as hair follicle (hair grow promoting agents), sebaceous or eccrine glands (anti-perspirant agents) or specific cell types such

Fig.1 - Different skin penetrability

Fig.2 – Chitin Nanofibrils at SEM

as melanocytes (depigmenting agents), Langerhans or Mast cells (immunostimulant and antiinflammatory compounds), can be targeted (Fig.1). So far, differently from drugs, it can be safely stated that the majority of current functional skin ingredients, and, first of all CN, are delivered to either the outer layer of the skin, viable the epidermis or dermis (i.e cosmetic dermal delivery) and not to the systemic circulation (i.e transdermal cosmetic delivery), being particularly safe for its cosmetic use. (Morganti P et al., 2007; Wiechers J.W, 2008; Biagini et al., 2008). At this purpose the natural chitin nanofibril (CN), processed and patented worldwide from MAVI Sud (MAVI SUD Int. Pat, 2005), seems to play many supporting roles in the cosmetic/personal care/pharmaceutical markets both as delivery system and active compound (Morganti P, 2007; Morganti et al., 2008; Mezzana P., 2008).

CLINICAL EFFICACYWhat is interesting to underline is the capacity the nanofibril has to increase the clinical efficacy of the active ingredients (Muzzarelli RAA, et al. 1999; ), positively affecting their partition coefficient between formulation and skin, when used in the right way and in the right emulsion (Morganti P, 2008). The prevalent amino groups of these rod-like and positively charged chitin crystallites, embedded in water form hydrogen and ionic bonds with different kind of molecules, originating innovative skin-friendly complexes contributing to the stability of the final suspension also (Fig. 2). These new obtained chitin-complexes reorganize theirselves spontaneously into large domains, easily emulsifying different class of lipids. In depending of the different quantity and quality of CN, CN-complexes and of other active compounds (natural and synthetic lipids, polymers and amphiphilic molecules), the emulsifiers selected and all the manufacturing process used, it is possible to obtain different tipology of emulsions (vesicular or lamellar, micro or nano) solubilization systems and gel systems (Fig.3).Moreover, the CN-complexes can be chosen from a wide variety of active compounds both idro and lipo-soluble to meet the needs of the application as well as the clinically efficacy of the final cosmetic formulation (Morganti et al., 2008; Mezzana P., 2008).

BIO-AVAILABILITYHowever, to increase the efficacy, safety and bio-availability of all the active ingredients applied to the skin, the interaction between vehicle/active ingredient, the capacity the vehicle has to produce changes in skin structure, and the doplet size of the vehicle, should be critically controlled. The small size ensures a closer contact with the SC and thus, the amount of incorporated active ingredients within the carrier reaching the programmed site of action will be notably increased. CN seems, in fact, to have the ability to induce the creation of a monolayer lipidic film on the SC, thereby

Fig.3 - different tipology of emulsions

Fig.4 – Chitin Nanofibril into the skin

increasing the skin penetration of all the active compounds, avoiding the excessive water evaporation and thus increasing skin hydration also.Moreover, when directly in contact with the stratum corneum, the emulsified CN may be hydrolized by the skin’ enzymes and transformed in dimeric and/or tretrameric units. Thus, oligomers may penetrate throughout the skin layers together with the eventually bonded active compounds.However, the influence of formulation design, the selected ingredients used together with CN, and the manufacturing process are other important factor to obtain a correct skin penetration.Therefore the CN, used alone or in combination with natural antioxidant and immunomodulant compounds may found interesting application, leading to a new generation of skin anti-aging and wound healing products.

OBTAINED RESULTSThus, our R&D group verified the cosmetic activity of CN by different studies both in vitro and in vivo ((Morganti et al. a, 2008; Morganti et al. b, 2008). These studies have stressed the influence CN has to increase the active compounds’ penetration through the stratum corneum and, thereby the viable skin (Fig. 4). As matter of fact, in vivo skin hydration increase from 40 (only CN vehicle) to 80% (CN + active compounds) (Tab.1), and surface skin-lipids increase also from 35 to 68%(Tab.2).On the other side TEWL decrease from about 50 to 72% and lipid peroxides from 35% to66% (Tab.3). It is interesting to underline the whitening activity CN seems to have also strongly decreasing the age spots appearance (Tab. 4). On the other hand the in vitro studies demonstrates as CN is capable to increase both fibroblast proliferation and the relative collagen production. Naturally the ATP production is also seems to increase by the activity of CN (Tab.5).

Tab. 1 Tab. 2

Tab. 5

CONCLUSION

These examples underline the activity CN seems to have as innovative cosmetic delivery , allowing particular bonds and connections between water, active molecules and the cells of both stratum corneum and viable skin. These CN bindings, seem to be mediated by a group of non covalent attractions (ionic and hydrogen bonds) that are individually quite weak, but whose energies can sum to create an effective force between two or more separate molecules.

CN, as a natural polysaccharide recognized from the cell components, may have different fates. Part, totally hydrolized may be used as monomer subunits to construct the giant polymeric macromolecules of the cell, such as large polysaccharides. Others, may act as energy sources and therefore, broken down and transformed into small molecules, in a maze of intracellular metabolic pathways. It is to remember that both glucosamine and acetyl-glucosamine are fundamental molecules of our body. In conclusion CN, as sugar- like compound , may be considered a safe molecule that, for its particular characteristics to easily bond water and other molecules, and to penetrate the different skin layers, may be useful not only as skin carrier, but also as an active component to formulate innovative cosmetic and pharmaceutical products. Many other seem also the possibilities of its use as, for example, to make innovative fibers for biofunctional textiles (Morganti P, 2008). For better understanding this fascinating rediscovered molecule it will be necessary to make further multidisciplinary studies, introducing new technology useful for ameliorate the general wellbeing. This is our challenge for the future.

Tab.3 Tab. 4

References

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MAVI SUD International Patent, 2005, PCT/IB2005/053576

Mezzana P., 2008, Clinical efficacy of a new chitin-nanofibrils based gel in wound healing . In print on: Acta Chirurgiae Plasticae

Morganti P, Lee Yuanhong, Morganti G., 2007, Nano-structured products: technology and future, J. Appl. Cosmetol., 25:161-178.Morganti P., 2007, Where nutriceuticals meet cosmecuticals, J. Appl. Cosmetol., 25:111-120

Morganti P., Fabrizi G., Palombo P., Palombo M., Ruocco E. Cardillo A and Morganti G., 2008, a. Chitin-nanofibrils: a new active cosmetic carrier. Journal of Applied Cosmetology 26: 105-120

Morganti P, 2008, Unpublished data

Morganti P., Morganti G., Fabrizi G. and Cardillo A, 2008, b. A new sun to rejuvenate the skin. In print on: Journal of Applied Cosmetology

Morganti P., 2008, Leather & Textile Chemicals Chitin nanofibrils in textiles. Speciality Chemicals Magazine 28 (n.9) :26

Muzzarelli RAA, Mattioli-Belmonte M, Pugnaloni A and Biagini G., 1999, Biochemistry, histology and clinical uses of chitins and chitosans in wound healing. In: Chitin and and Chitinases P.Jollés and RAA Muzzarelli, eds. Birkhaüser Verlag Basel/Swizterland, p. 251-264

Muzzarelli R.A.A. and Muzzarelli C., 2005, Chitin nanofibrils. In: Chitin and Chitosan: Research Opportunities and Challenges P.K. Dutta and RAA Muzzarelli, eds. New Age International, New Dehli, India

Wiechers J.W 2008 Science and application of skin delivery systems. Allured Ed, Carol Stream, IL,USA