2003 ANNUAL SCIENTIFIC MEETING TOPICAL VITAMIN E: WHAT FORM AND HOMOLOGUE OF TOCOPHEROL MATTER? Brent Flickinger, Ph.D., J. J. Mathieu and Janice Binger Archer Daniels Midland, Decatur, IL Titis review focuses on personal care products containing vitamin E and the implications of the vitamin E form on topical antioxidant efficacy. Tocopherols are a primary lipophilic antioxidant with the capability of breaking the chain involved in the propagation of free radicals. Tocopherols are particularly reactive with peroxyl radicals which have been identified as important mediators of oxidation of polyunsaturated fatty acids within membrane phospholipids. Depending on conditions, different tocopherols may have different antioxidative capacities. From a nutritional and physiological viewpoint, alpha-tocopherol is preferentially retained within the body which has resulted in its recent identification as the sole tocopherol possessing nutrient essentiality. This metabolic difference in tocopherol isoforms is due to the presence of alpha-tocopherol transfer protein in the liver which is highly specific in binding alpha-tocopherol. From a skin viewpoint, the epidermis maintains alpha-tocopherol as the most important vitamin E isoform quantitatively. Many cosmetic and skin care products include vitamin E as part of their formulation. Mintel' s Global New Product Database (GNPDB) lists approximately 4,500 skin care products, alone, containing vitamin E. Most products list alpha-tocopheryl acetate as the vitamin E ingredient with very few products containing mixed tocopherols which includes non-alpha-tocopherols such as gamma-tocopherol and delta-tocopherol. Alpha-tocopheryl acetate is the preferred choice in a product formulation. Alpha-tocopheryl acetate is non­ reactive and stable maldng it more reliable for maintaining a shelf-stable product. Typical incorporation rates of alpha-tocopheryl acetate are relatively minor. Several studies using topical applications containing alpha-tocopherol have shown that the alcohol form appears to be more effective than the acetate ester form in protecting skin against the damage from UV irradiation. Also, in topical applications, the tocopheryl acetate form of vitamin E appears inert and ineffective in several reports. Similarly when ingested, tocopheryl acetate is hydrolyzed by the gut to the active alcohol form of vitamin E which is absorbed into the body. However, the difference between the activities of alcohol and acetate ester forms in topical applications continues to be a topic of considerable debate with dose, duration, bioavailability, formulation and UV exposure all being potentially important considerations. Consistently, non-alpha-tocopherols are present in skin to varying degrees ranging from 10-20% of total tocopherols (1, 2, 3). In human skin, a recent report suggests that the ratio of alpha-tocopherol to gamma­ tocopherol is approximately 10-to-l which is typical of the ratio found in serum ( 4 ). Levels of alpha­ tocopherol and gamma-tocopherol correlate well with the skin's ability to scavenge free radicals but not with the ability to protect against doses of UV that cause sunburn indicating that tocopherols alone may not individually determine photosensitivity. An earlier report in the literature suggests that topical application of non-alpha tocopherols (gamma and delta) appear to provide skin protection from UV to an equal degree as alpha-tocopherol as measured by thymine dimer formation using a mouse skin model (5). This result suggests a potential opportunity for utilization of adding non-alpha-tocopherols in skin care product formulations. Potential non-antioxidant actions of alpha-tocopherol may have a role for maintaining skin health. Alpha-tocopherol has been identified to inhibit protein kinase C (PKC) in a non-antioxidant manner using an in vitro model system (6). Further utilization of an in vitro model system has demonstrated the ability of alpha-tocopherol to inhibit the expression of connective tissue growth factor (CTGF) (7). CTGF mRNA expression has been shown to be constitutively active in normal human skin (8). Using a model in vitro system of normal hwnan skin cell types constitutively expressing CTGF mRNA and protein, ultraviolet irradiation results in inhibition of CTGF mRNA. Alpha-tocopherol may assist in promoting skin health by nonnalizing CTGF expression following UV exposure due to the role of CTGF in stimulating synthesis of procollagen thus impacting the extracellular matrix. References I. Cancer Epidemiol Biomarkers Prev, 2, 145, (1993). 2. J Invest Dermatol, 110, 756, (1998). 3. J Invest Dermatol, 113, 1006, (1999). 4. Free Radie Biol Med, 34, 330, (2003). 5. Mo/ Carcinog, 24, 169, (1999). (mcvean) 6. Biochem Mo/ Biol Int, 41, 93 (1997) (fazzio) 7. Circ Res, 92, 104, (2003) (villacorta) 8. J Invest Dermatol, 118, 402, (2003) (quan) 221

222 JOURNAL OF COSMETIC SCIENCE CLEANSING AND RELEASE BY NOVEL NANOGEL CARRIERS Ponisseril (Som) Somasundaran, Ph.D., F. Liu, D. Sarkar and C.C. Gryte National Science Foundation I/UR Center, Langmuir Center for Colloids and Interfaces Columbia University, New York, NY 10027 There is an ever-increasing need for environmentally benign cosmetic ingredients that can be released at slow rates. Design of personal care products for desired release of actives or removal of undesired secretions involves transport of the carrier onto the skin or the hair, deposition in response to dilution or changes in pH, temperature or salinity and release of the actives at a controlled rate. New polymer nanogels provide an efficient means to fulfill these requirements when appropriately modified to interact with the desired actives. Polyacrylamide nanogels, a type of nanosized, cross linked particles, have been synthesized towards this purpose using inverse microemulsion polymerization. These water-soluble, sponge-like nanogels are very small in size (50 nanometers) and have vast amounts of interstitial space between the polymer chains. To make them more specific and efficient, a series of chemical modifications were carried out by firstly copolymerizing ofN-acryloxysuccinimide into PAM structure and secondly using the activity ofsuccinimide to substitute various chemical functions into the nanogel structure. In addition, amide on the PAM was hydrolyzed to pendant carboxylic acid group, these methods permit the introduction of hexyl groups, ionic glycine and acrylic acid (anionic) and their combinations. The resultant functional nanogels and the unmodified nanogels were characterized in terms of swelling abilities, hydrophobicity and charge density. The physical properties of nanogel particles were changed significantly by the introduction of such functional groups. Active encapsulation experiments using 3-( 10, 11-dihydro-5H-dibenzo [ a,d] cycloheptene-5-ylidene )-N,N­ dimethyl-1-propanamine hydrochloride (C20H23N·HC1), a compound with hydrophobic and ionic groups and pyrene, that is hydrophobic, as target molecules were carried out with these nanogels. As can be seen from Figures 1 and 2, the nanogels chemically modified for hydrophobicity and/or electrostatic charge show markedly higher ability for active binding when compared to the unmodified nanogels. While Figure 1 shows the binding of the organic active as a function of crosslinking density, Figure 2 shows I/I 1 , a fluorescence parameter indicating the hydrophobicity around the pyrene molecules in the nanogels. 1/11 varies from 0.6 to 1 as a function of non-polarity. It can be seen that the nano gel is hydrophobic and the modification with hexyl groups increases the hydrophoibicity and thus the potential for uptake of organic materials. The polymeric repeat unit composition and the type of pendent groups on the polymer matrix of the nanogel are crucial for determining the degree of swelling and the capacity of the nanogels. Nanogels with different crosslinking densities were also prepared by inverse microemulsion polymerization and were modified by attaching hexyl and/or carboxylic acid groups to the polymer backbone. The effects of cross linking density on the structure of the polyacrylamide nano gel particles investigated by dynamic and static light scattering measurements, suggested that the swelling abilities of the nano gel particles strongly depend on the degree of the cross linking density. At high crosslinking density, the structure of the nanogel particle can be described as a rigid sphere. With the decrease in crosslinking density the nanogel particles tend to be flexible random networks. The crosslinking density proves to be important factor for active encapsulation abilities of nanogels, especially for large organic molecules. Active binding with nanogels to some extent, depends not only on the interaction between the organic molecules and the polymer backbone but also on the diffusion of the organic molecules inside the nano gel network. The highly crosslinked nano gels usually have compact structure with small particle size and might sterically exclude the large molecules. As the crosslinking density is decreased, the particles become less compact which makes the interior accessible for large molecules and thus the binding efficiency is increased.