The effectiveness of an innovative biorevitalizing mixture carried by the transdermal electrodelivery

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J. Appl. Cosmetol. 24, 1-6 (January/March 2006) The effectiveness of an innovative biorevitalizing mixture carried by the transdermal electrodelivery P. Forgione', F. De Natale', E. Sammarco', N. Chianese', P. Vitiello' ' U.O. Dermatologia - P.O. Cardinale Ascalesi -ASL NA l,napoli - ltaly ' Physician. Napoli - ltaly Received: March, 2006. Presented at the 5 National Congress A.O.MG. "/ colori della Dermatologia", Capo Rizzuto (KR), ltaly, October 6-8, 2005 Key words: Hyaluronic acid; Betaglucan: Vitamic C: Electroporation: Skin aging: Summary Today dennatologists have at their own disposal many therapeutical devices able to satisfy the common desire of many of their patients to rejuvenate their skin reducing and slowing down signs of the time passi ng by. We report our experience in us ing a biorevitalizing mixture of hyaluronic acid, vitamin C and betaglucan (trade name HCG2000 ) properl y carried by electroporation, a non-invasive innovative technique useful in the treatment of face and body skin imperfections. Riassunto Sono ormai a disposizio ne del dermatologo numerosi presidi terapeutici in grado di soddisfare il comune desiderio di molti pazienti di ringiovanire la propria pelle rid ucendo e rallentando i segni del tempo.riportiamo la nostra esperienza nell' utilizzo di una miscela di biorivitalizzanti (denominata HCG2000 ) costituita da acido ialuronico, vitamina Ce betaglucano opportunamente veicolata attraverso l'elettroporazione, tecnica innovativa non invasiva utile nel trattamento degli in estetismi del volto e del corpo.

The effectiveness of on innovative biorevitalizing mixture carried by the transdermal electrodelivery INTRODUCTION The solution* used is a calibrated mixtu re of biostimulant acti ves of proved effecti veness such as betaglucan, vitamin C arg inate, and hyaluronic acid, which stimulates the cellular turnover and the synthesis of collagen, elastin and fibrin. It is indicated in the treatment via injection of stretch marks, wrinkles and acne scars. The transdermal electroporation is a methodology that by using peculiar electrical pulsating impulses, cause a temporary expansio n of intercellular spaces allowing a fast and selecti ve penetration of drugs and dermocosmetics into the skin basai layer (1,2,3,4). We report our experience in the use of HCG2000 by electroporation on subjects showing chrono and photo-induced facial skin aging. MATERIALS ANO METHODS For this study it has been used a cytostimulant solution* conta ining: I) hyaluronic acid 2) betaglucan 3) ascorbic acid dissolved in sterile solution in phials of2 and 5 ml. For each treatment we used J,5 ml of the solution dissolved in a wire gel. The obtained mixture was io nized in a specific metallic acti vation room who m which the e lectronic device called Matripor (Burattini B io medica! Engineering, Pozzuoli, NA) is equipped. This allows a fast passage of the used molecules through the pulsed electrical waves of low frequency and high intensity, generated by this special device. The study was conducted on 30 women aged between 40 and 55, treated by a 16 minutes electroporation sitting once and twice a week. RESULTS After 10 treatments a clear reduction in wrinkles depth was observed, many of which just after 5 weeks of treatment. Moreover it was observed a remarkable increase in skin hydration and tone. After the transdermal application of the mi xture none of the subjects showed undesirable effects. The persona! opin ion of the subjects treated was positive in all cases and extremely positi ve for the 50 % of the cases. DISCUSSI ON The calibrated combination of the three active principles, betaglucan, vitamin e and, hyaluronic acid, that notoriously sti mulate and speed up the synthesis of the normai fibrous co mponent of the skin, optimizes the normai production of collagen, elastin and fibrin (5,6,7). This association, thanks to a patented special procedure, permits the creatio n of particular ionie bonds activating the different molecules that allow and help their delivery and penetration though the different skin layers. In this way hyaluronic acid can work with its electi ve re-hydrating activity maintaining and linking water in skin tissue (8). The salification of vitamin C makes it stable against the oxidative processes, exalting at the same time its peculiar anti-free radicals activity as well as its stimulati ng activity in collagen synthesis (9,10). Finally, betaglucan, strong and well known activator of the skin immune system, works both stimulating the cellular tum over and fighting oxidative stress. The biorevitalizing mixture we used, is normally injected intradermically or intraepidermically in the desired quantity in the areas to be treated in a rigorous asepsis conditions. *trade name HCG2000 2

P. Forgiane, F. De Natale, E. Sammarco, N. Chianese, P. Vitiello Periocular Wrinkles Before After 10 sittings Periocular Wrinklcs Beforc Aftcr 10 sillings Glabellar Wrinkles Before After 10 sittings Fig,J 3

ssm111s 8 JOJJ'v' OJOJ0 8 SO()fUl.lJ\'\.11l[(Oqll(Q SSU!Jl!S 8 JOJJ'v' J.1a1111apo1pa1a /OWJBPSUOJJ Bl.{J J.q PBfJJO;J BJnJXIW BUIZ!JOJfllBJOlq BlllJOllOUUf uo JO ssaua111pajja Bl.{1

P. Forgiane, F. De Natale, E. Sammarco, N. Chianese, P. Vitiello The injection exposes the patient to a possible appearance, in the injection area, of erythema, swelling, pain, itching and microhaematomas. The electroporation uses a reversible electric field, with short and high voltage pulses through which it electropores the double layer lipidic barriers with formation of subcellular pores that increase remarkably the substances delivery speed, even if of high molecular weight. This methodology increases the sbn penetration of the active compounds, allowing a higher absorption rate, eliminating possible side effects due to the intradermal or intraepidermal injection and speeding up their therapeutic effects. The obtained results, reported in the figures 1-6, confirm that electroporation is an effective and well tolerated methodology to treat skin ageing and skin photo-ageing by using biorevitalizing molecules. ACKNOWLEDGEMENTS The authors would like to thank Mavì Sud S.r.l. for the samples of HCG2000" provided and Mr. Gianfranco Burrattinifor the Matripor" project. 5

The effectiveness of on innovative biorevitolizing mixture corried by fhe fronsdermol electrodelivery References 1) Tsong TY. (1991). Electroporation of celi membranes. Biophys J, 60:297-306 2) Rabussay R, Dev NB, Fewell J, Smith LC, Widera G, Zhang L. (2003). Enhancement of therapeutic drug and DNA delivery into cells by elettroporation. J. of Physics D: Applied Physics, 36 (4):348-363 3) Zhang L, Li L,An Z, Hofmann GA. (1997). In vivo transdermal delivery of large molecules by pressare-mediatad electroincorporation and electroporation: a nove! method for drug and gene delivery, Bioelectrochemistry and Bioenergetics, 42:283-292 4) Santoianni P. (2005). Intradermal delivery of acti ve principles: field of dermatologica! research. ltalian J Dermatol Venereol,140:539-56 5) Burke K. (2002). Photodamage of the skin: protection and reversal with topica! antioxidants. J Cosm Derm, 3 (3): I 49-ss 6) Karam P. (2002). Non-invasive skin rejuvenation techniques. J Cosm Denn, 1 (2): I 05-ss 7) Kockaert M, Neumann M. (2003). Systemic and topica! drugs for aging skin. J Drugs Dermatol, Aug; 2(4): 435-41 8) Andre P. (2004). Hyaluronic acid and its use as a "rejuvenation" agent in cosmetic dermatology. Semin Cutan Med Surg, Dee; 23(4):218-22 9) Farris PK. (2005). Topica! vitamfo C: a useful agent for treating photoag ing and other dermatologie conditions. Derma/o/ Surg, lui; 31 (7 Pt 2):8 14-7, discussion 8 18 10) Humbert PG, Haftek M. (2003.) Topica! ascorbic acid on photoaged skin. Clinica!, topographical and ultrastructural evaluation: double-blind study vs. placebo. Exp Dermarol, Jun; 12 (3):237-44 Author Address: Dr. Patrizia Forgione Via Stendhal 14 80133 Napoli Email: forgionepatrizia@virgilio.it 6