94 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS O . O ' 8•.o i i ! Figure 8. Stability of vitamin E in receptor solution without contacting skin: Chromatograms of samples in UV and radioanalysis at 24 hours. CONCLUSION Percutaneous absorption of vitamin E has been investigated. The radiolabeled vitamin E promptly penetrated the skin while nonlabeled vitamin E appeared after a long time lag. HPLC analysis in line with UV and a liquid scintillation counter showed that vitamin E was extensively metabolized to ot-tocopherol quinone and more hydrophilic metabolites in the hairless mouse skin. Since vitamin E undergoes significant metabo- lism during skin permeation, the data with radiolabeled vitamin E does not necessarily represent the characteristics of intact vitamin E itself. Total radioactivity has to be identified from the possible metabolites. ACKNOWLEDGMENTS The authors express thanks to Professor Richard Chang and Dr. Allan Cooney in the Chemical Biology Laboratory, College of Pharmacy, Rutgers University, for their valu- able discussions and kindness in providing HPLC in line with LSC for this study. The radiolabeled ot-tocopherol and ot-tocopherol quinone standaMs offered by Dr. L.J. Machlin of Hoffmann-La Roche, Nutley, New Jersey, are greatly appreciated. A grad-
VITAMIN E METABOLISM 95 uate research fellowship to Ae-Ri Cho Lee from Senju Pharmaceuticals, Osaka, Japan, is gratefully acknowledged. REFERENCES (4) (5) (6) (7) (8) (9) (10) (ll) (12) (13) (14) (15) (1) H. M. Evans, O. H. Emerson, and G. A. Emerson, The isolation from wheat germ oil of an alcohol ot-tocopherol, having properties of vitamin E, J. Biol. Chem., 113, 329-332 (1936). (2) E. H. Grugen, Jr. and A. L. Tappel, Reaction of biological antioxidants: 111. Composition of bio- logical membranes, Lipids, 6, 147-148 (1971). (3) H. M. Tinberg and A. A. Barber, Studies on vitamin E action: Peroxidation inhibition in structural protein-lipid micelle complexes derived from rate liver microsomal membranes, J. Nutr. Res., 100, 413-418 (1970). D. Djerassi, L. J. Machlin, and C. Nocka, Vitamin E: Biochemical function and its role in cosmetics, Drug and Cosmetic Industry, 46 (March 1986). M. Kakimura and T. Matsuzawa, Percutaneous absorption of ot-tocopherol acetate, J. Vitaminol., 14, 150-159 (1968). G. J. Klein, Dermal penetration and systemic distribution of 14C-labeled vitamin E in human skin grafted athymic nude mice, Internat. J. Nutr. Res., 59, 333-337 (1989). R. J. Scheuplein, Mechanism of percutaneous absorption: 1. Routes of penetration and influence of solubility, J, Invest. Dermatol., 45, 334-346 (1965). J. G. Bieri and R. P. Evarts, Tocopherols and polyunsaturated fatty acids in human tissues, Am. J. Clin. Nutr., 28, 712-720 (1975). J. G. Bieri and T. J. Tolliver, On the occurance of ot-tocopherol quinone in rat tissue, Lipids, 16, 777-779 (1981). H. E. Gallo-Torres, Intestinal absorption and lymphatic transport of dl-3,4-[•H]2-ot-tocopheryl nic- otinate in the rat, Internat. J. Vit. Res., 40, 505-513 (1970). J. lmai, M. Mayashi, S. Awazu, and M. Hanano, Solubilization of dl-ot-tocopherol by bile salts, polysorbate and egg lecithin. Chem. Pharm. Bull., 3, 4077-4082 (1983). K. Tojo, C. C. Chang, U. Doshi, and Y. W. Chien, Stratum corneum reservoir capacity affecting dynamics of transdermal drug delivery, Drug. Dev. Ind. Pharm,, 14, 561-572 (1988). H. E. Gallo-Torres, "Blood Transport and Metabolism," in Vitamin E.' Comprehensive Treatise, L. J. Machlin, Ed. (Marcel Dekker Inc., New York, 1980). C. D. Yu, Prodrug-based topical delivery: Simultaneous skin transport and bioconversion. Ph.D. thesis, The University of Michigan (1978). A. R. C. Lee, Percutaneous absorption and bioconversion of a provitamin for vitamin C and exper- imental and mathematical study on simultaneous diffusion and bioconversion, Ph.D. thesis, Rutgers- The State University of New Jersey (1990). (16) T. Shiratori, Uptake, storage and excretion of chylomicra-bound [•H]-tx- tocopherol by the skin of the rat, LiJ• Sciences, 14, 29 (1979).
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