2005 ANNUAL SCIENTIFIC SEMINAR S 2 s 2 1 - 1 3 Figure 1: Schematic block representation of the protein polymer SELP47K 353 SELP4 7K consists of four silk repeat peptides, seven elastin repeat peptides, and one lysine modified elastin repeat peptide. The latter peptide introduces a potential cross-linking functionality and opportunity for additional chemical modification. This modification also increases the water solubility of the polymer and imparts cationic character for improved substantivity. Results from in vitro studies indicate that SELP4 7K offers unique properties such as self-assembling nanofiber formation, mechanical strength, and hydrogel matrix development [2]. Additionally SELP4 7K stimulates human dermal :fibroblast cells in-vitro to produce elastin in a dose dependent manner. (Figure 2) [3]. We hypothesize that self-assembling nano:fibrillar networks of SELP4 7K relay a signal to fibroblasts to improve their elastin production. 480 JSO 1111 J■ 250 i! ., 150 1111 ,. m !I' 50 _,. 0 -50 Media only Untreated 0.1'1,SELP 0.5% SELP 1.0'I, SELP Figure 2: In-vitro assay of elastin production using dermal fibroblast cells References: 1) Kumar M, Cuevas WA: Use of repeat sequence protein polymers in personal care compositions, US Patent Application Publication No. US 2004/0180027Al. 2) Kumar M, Mazeaud I, Christiano SP: Controlled release of active agents utilizing repeat sequence protein polymers, US Patent Application Publication No. US 2004/0228913Al 3) Collier CD, Kumar M, and Cuevas WA: Repeat sequence protein polymer, active agent conjugates, methods and uses, US Patent Application Publication No. US 2004/0234609Al.
354 JOURNAL OF COSMETIC SCIENCE SKIN LIGHTENING AND ANTI-AGING INGREDIENTS How ARE THEY INTERLINKED? Ratan K. Chaudhuri, Ph.D., Germain Puccetti and Zoia Lascu EMD Chemicals, Inc., Hawthorne, NY 10532 (An Affiliate of Merck KGaA, Darmstadt, Germany) The pigmentation of the skin, due to synthesis and dispersion of melanin in the epidennis, is of great cosmetic and societal significance. It is also the key physiological defense against sun-induced damage, such as sunburn, photoaging and photocarcinogenesis. This presentation focuses on polyphenolics of natural origin having both skin lightening and anti-aging effects and their mechanistic interlink which provides these two desired skin benefits. Photoaging & Melanogenesis: The unifying pathogenic agents responsible for photo-damage are UV­ generated Reactive Oxygen Species (ROS) that deplete and damage the enzymatic and non-enzymatic antioxidant defense systems of the skin, and the release of matrix metalloproteases (MMPs) such as MMP- 1 and MMP-3, that damage the extracellular matrix proteins1 The drastic long-term effects of UV on the skin include photoaging, characterized histologically by solar elastosis due to degradation of collagen and the accumulation of abnormal elastin in the dermis, and skin cancers. ROS, especially, superoxide anion has been shown to activate tyrosinase thereby increasing pigmentation. Quenching of superoxide anion can also lighten skin2. Melanin forms through a series of oxidative reactions involving tyrosine in' the presence of tyrosinase. It has been shown that cells, such as, eosinophiles, neutrofiles and mast cells are capable of synthesizing melanin without the presence of tyrosinase. Okun et al were also able to show a correlation between peroxidase-H2O2 activity and its ability to oxidize tyrosine or DOPA to melanin3 There is no doubt that DOPA can be a good oxidizable substrate for peroxidases and it has recently been reconfirmed that the peroxidase-H2O2 system alone is capable of converting DOPA and dopamine to melanin. The ability of the peroxidase-H2O2 system to promote the oxidative polymerization of 5, 6-dihydroxyindole and 5, 6-dihydroxyindole-2-carboxylic acid to melanin pigments has also been demonstrated. Recently, the role of NO and Fe2+/I-{zO2-induced melanogenesis have been demonstrated4 . The later reaction is known as Fenton reaction, which is responsible for generating ROS and thus causing photo-damage to skin. Cause and consequences of UV-Induced skin damage and their interlinking to melanogenesis can be schematically represented in Figure 1. Release of Free Iron & Copper DNA Strand breakage Mutations Protein UV Light Reactive Oxygen Species Skin Damage Lipids SH oxidation L Peroxidation Deactivation of enzymes Increase in Melanogenesis Release of Matrix Metalloprotease Carbohydrate L Depolymerization of hyaluronic acid Figure l: Cause & Consequences of UV-Induced Skin Damage and their Interlinking to Melanogenesis
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