2005 ANNUAL SCIENTIFIC SEMINAR Conclusions The topical application of the ozone stressed yeast extract protects the Epidenn tissue against oxidative damage to both DNA and cholesterol, but not to degradation of melanin in the Melanodenn model. Graph 1. DNA Damage 8-0xoguanine (ng per microgram DNA) . . ...... .......................... . .....,-.... ...... ............... .... _,, __ ... Graph 2. Cholesterol Damage En.c:t al ozone on cholesterol levels In nalild and ilon-lnllacl full lhlcknaa ..... madela. 349 +-----lf.1-----1-­ .,___ ....... : ::,__�-­ •:• +----1:•:t---l).)J- m-1---------------.........................-................-14) T •'• +--a::11=---t: :t--�l- -: I -: . • • -•�•- 2 --If--- :::+---b.�,- 1 � 111111 � /1---fi"i:'1--- ♦ ♦ ♦ • -•�••__: ♦ ♦ ♦ • ffJ�B � 4J Ii i � -----.--........,......,-- -- , ... n..... ,.,_ ,.,_ ,.,_ 5'1.0ano - - - s- - - - - Treatment Graph 3. Melanin Damage !I 6.0 I s.o r 4.o F� !f 1.0 0.0 Rererences Melanin: ug/mg tissue weight 1% Ozone Stressed 1 rrMTrolox TrNtffllllt, PBS f'al-Ozone Ellposed I. Gafliter JS, Marley NA. Sci World J 3 (2003) 199. �,:'/ 2. US Environmental Protection Agency website: www.epa:gov/airtrends/ozone.htm1. 3. Weber SU, Han N, Packer L. Curr Prob/ Dermatol 29 (2001) 52. 4. Thiele JJ, Traber MG, Polefka TG, Cross CE, Packer L. J Invest Dermatol 108 (1997) 753. 5. Thiele JJ, Traber MG, Tsang K, Cross CE, Packer L. Free Rad Biol Medl3 (1997) 385. 6. Helbock HJ, Beckman KB, Ames BN. Methods Enzymoi 300 (1999) 156. 7. Dohm MR, Mautz WJ, Andrade JA, Gellert KS, Salas-Ferguson LJ, Nicolaisen N, Fujie N. Environ Toxicol Chem 24 (2005) 205. 8. Wentworth P, Nieva J, Takeuchi C, Gaive R, Wentworth AD, Diley RB, DeLaria GA, Saven A, Babior BM, Janda KO, Eschenmoser A, Lerner RA. Science 302 (2003) 1053. 9. Smith LL. Free Rad Mo/ Biol 31 (2004) 318. IO. Tavakkol A, Nabi Z, Cardona S, Soliman N, Polefka T. J. Invest Dermatol 114 (2000) 844. 11. Thorpe GW, Fong CS, Alic N, Higgins VJ, Dawes IW. PNAS 101 (2004) 6564. 12. Venkatesan VP, Gruber JV. Spec Chem Mag 24 (2004) 19. 13. Hinze H, Prakash D, Holzer H. Arch Microbiol 141 (1987) 105.

350 JOURNAL OF COSMETIC SCIENCE LAMELLAR DELIVERY SYSTEM FOR TARGETED DELIVERY INTO THE SKIN Nava Dayan, Ph.D. Lipa Chemicals, Inc., Paterson, NJ 07504 The diversity of applications in cosmetics creates the need to target different compounds into sub-tissues of the skin. While, for example, moisturizers need to be retained in the upper layer of the skin, anti-aging active compounds need to reach the epidermis-dermis junction. An appropriate delivery system will enable better targeting of a compound to its site of action in the skin, while reducing the concentration needed to achieve an effect, and thereby elevating its safety. We present a novel microscopic lamellar delivery system (MLDS) that can be tailored to target active compounds to sub-tissues in the skin. This patent pending technology blends specific lipophilic compounds that when combined with water in certain ratios create unique microscopic structures. The composition and processing determines the physical properties of the delivery systems created. Transmission electron microscopy resulted in the observation of three major structures. It is hypothesized that each of those structures will interact differently with the skin, and allow penetration to the different layers. Skin permeation studies will be conducted to substantiate the hypotheses. The importance of targeted delivery Mammalian skin is an excellent barrier for the penetration of compounds. Its upper layer, the stratum comeum, has a special organization where the dead comeocytes are cemented by intercellular lipid lamellae that are covalently linked to the cell membrane (1). The intercellular lipid lamellae are composed of cholesterol, cholesterol derivatives, free fatty acids and ceramides, with the latest being the main constituent (around 50%). Those lamellae are derived from granules, which secrete their content to the intercellular spaces of the upper layer. They include lipids, hydrolytic enzymes and several other proteins (2). The skin is a multi-layered organ, in which every layer displays diverse composition and properties, and is responsible for different functions. Therefore, when treating the skin, it is crucial to assure that the active ingredient in the applied formulation will reach its target. While sunscreen formulations, for example, should be designed to protect the upper layer of the skin, formulations that include skin-lightening actives should reach the living epidermis. Tailoring an appropriate delivery system can not only enable targeting the active compound to its site of action, but also control its time of residence and release, hence, improve its bioavailability and broaden the therapeutic index for safety. Lamellar delivery systems - short overview Studies have demonstrated that the stratum comeum lipid organiz.ation can be imitated with model lipid mixtures based on isolated stratum comeum lipids (3). Other systems that were composed of different combinations of cholesterol, fatty acids and ceramides were used as models to test for skin permeation of compounds (4). Close shaped lamellar systems that are being used as delivery systems for the skin are vesicular systems. Throughout the past two decades scientists have designed a variety of vesicular systems that are meant to embody the active compound in its compartments and carry it (5,6). It was found that while classic multi-lamellar phospholipid made Iiposomes tend to create a reservoir of the entrapped compound in the upper layer of the skin, special flexible vesicles were demonstrating penetration to deeper layers and even allow for transdermal delivery (7). The common concept behind the design of these systems is to compose an intact relatively stable system that will transmit the active to or through the skin while reversibly changing the stratum comeum barrier properties, and preferably protecting the active compound.