2005 ANNUAL SCIENTIFIC SEMINAR Microscopic lamellar delivery system- hypothesis and rationale MLDS technology suggests a novel approach, applicable mainly in the area of cosmetic and personal care, but also with potential applications in trandermal delivery. As already mentioned, the skin is considered to be multi-compartment organ in which every compartment (i.e., sub-tissue) is a target for a variety of actives used to treat the skin. The MLDS system, as oppose to previously describe lamellar systems, is used as a "key" to open pathways in the stratum comem, and not necessarily as a carrier. This is a dynamic system. Negative staining transmission electron microscopy observation showed that the system is composed of three major lamellar structures that are most likely to exist in equilibrium. By changing the percentage of components in the system, and its way of preparation, one can create a situation in which one structure will dominate on the other two. The three structures are: intact vesicles, with an average size of 100nm, ruptured vesicles (with loose unilammelar membrane) and lamellar sheets (see figure number I). Based on these structures properties and the understanding of their possible interactions with the skin, it is hypothesized that each system wilJ allow penetration to different sites in the skin. When changing its composition and creating a system where one structure will dominate the others, not only will it affect the skin intercellular lipids differently, but it will change the active's dissolution properties, its partitioning and diffusivity into the stratum comeum and hence its penetration profile. Figure number I: Three structures were found in the MLDS system, existing in equilibrium (from left to right): intact vesicles, ruptured vesicles and lamellar sheets Future studies Differential scanning calorimetry (DSC) will be conducted to follow thermodynamic changes in the system. While moving from organized intact vesicles towards lamellar sheets, alterations in the transition temperature are expected. In vitro skin penetration studies with marked delivery system will allow to study the correlation between the system structure and its interaction with the skin. References I. Cevc G. Self regulating smart carriers/or non-invasive and targeted drug delivery. Cell. Mo/. Biol. Lett. 7, 224-225, (2002). 2. de Jagerl M.W., Gooris G.S., Dolbnya J.P., Ponec M., Bouwstra J.A. Modeling the stratum corneum lipid organization with synthetic lipid mixtures: the importance of synthetic ceramide composition. Biochim. Biophys. Acta 1664, 132-140, (2004). 3. de Jager2 M.W., Gooris G.S., Dolbnya J.P., Bras W., Ponec M., Bouwstra J.A. Novel lipid mixtures based on synthetic ceramides reproduce the unique stratum corneum lipid organization. J. Lipid Res. 45, 923-932, (2004). 4. Hill J.R., Wertz P.W. Molecular models of the intercellular lipid lamellaefrom epidermal stratum corneum. Biochim. Biophys. Acta 1616, 121-126, (2003). 5. Bouwstra J.A., Honeywell-Nguyen P.L. Skin structure and mode of action of vesicles. Adv. Drug De/iv. Rev. 54, 41-55, (2002). 6. Yarosh D.B. Liposomes in investigative dermatology. Photodermatol. Photoimmunol. Photomed. 17, 203-212, (2001). 351 7. Dayan N., Touitou E. Carriers/or skin delivery o/Triethexyphenidyl HCI: Ethosomes vs. liposomes. Biomaterials. 21:18, 1879-1885, (2000).
352 JOURNAL OF COSMETIC SCIENCE SILK-ELASTIN PROTEIN POLYMER: A MULTIFUNCTIONAL ACTIVE INGREDIENT FOR SKIN (ARE Manoj Kumar, Ph.D. Genencor International, Inc., 925 Page Mill Road, Palo Alto, CA 94304 Abstract Biotechnology based products for personal care applications are appearing in the market place. These products fall into several categories: (i) peptides or small proteins, (ii) unique proteins and (iii) catalytic proteins (enzymes). Genetic and protein engineering enables us to engineer and produce protein polymers with multiple domains that can be selected for their unique properties and assemble them together to impart desired functions. This podium presentation will illustrate a new concept of hybrid proteins designed to deliver multifunctional activity in personal care formulations. We will describe studies (in vivo and in vitro models) of a novel silk-elastin protein biopolymer as a new functional active ingredient for skin care that has properties of both silk and elastin. This unique protein not only delivers soluble silk and elastin, but also many functional attributes, which are useful in skin care applications. Introduction Advances in genomic research offer a unique opportunity to design proteins with specific, targeted properties, that are important for providing specific benefits and that can then be produced consistenetly via fermentation. Additionally, multiple peptide motifs can be engineered to provide protein-based multifunctional biomaterials. Interest in repeat sequence protein-based polymers (RSPPs) has grown because this new class of biomaterials simulates naturally occurring ones, and can be modified for desired function for applications in personal care. Protein engineering offers the ability to screen for desired properties utilizing the tremendous potential diversity of amino acid combinations and fermentation allows for large-scale manufacturing. Using recombinant methods, one can precisely control and incorporate the molecular weight, size, stereochemistry, and functional distribution of active domains in the biopolymer to create self-assembling composite functional biopolymers for personal care applications. Using the twenty natural amino acids, one can create RSPPs designed for a specific function( s ). Subsequent chemical/biological modifications of amino acid side chains with a variety of functional groups further offers a means for incorporating specificity and variety in function. Multifunctional bioengineered personal care peptide ingredients can be created that will serve as a new paradigm for a protein-based personal care delivery platform. RSPPs produced though molecular biological design and fermentation, targeted to incorporate the needed characteristics for personal care applications, have been investigated (1 ). Representative examples of natural small peptide-based RSPPs and their block copolymers (repeated amino acid sequences,), include elastin, silk fibroin (GAGAGS), byssus (GPGGG), flagelliform silk (GPGGx), dragline silk, collagen, and keratin. The relative stability of these families of structural proteins in combination with their biocompatibility, and unique mechanical properties, provide the foundation on which one may exploit naturally derived RSPPs for wide-ranging personal care applications. RSPPs are similar to a chemically polymerized block of copolymers but do not have any heterogeneity. They are unique, defined, monodispersed, and have molecular weights that generally range between 30 kD and 250 kD. For example, in a RSPP named SELP4 7K (silk elastin like protein Unit block structure: Figure 1), individual units are composed of silk fibroin (S = GAGAGS), and elastin (E = GVGVP), and a lysine modified elastin peptide, K(GKGVP).
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