MEASURING TURNOVER TIME 331 REFERENCES (1) R. Marks, D. Black, I. Hamami, A. Caunt, and R. J. Marshal, A simplified method for measure- ment of desquamation using dansyl chloride fluorescence, Brit. J. Dermatol., 111, 265-270 (1984). (2) A. Y. Finlay, R. J. Marshal, and R. Marks, A fluorescence photographic photometric technique to assess stratum corneum turnover rate and barrier function in vivo, Brit. J. Dermatol., 107, 35-42 (1982). (3) D. Roberts and R. Marks, The determination of regional and age variations in the rate of desquama- tion, J. Invest. Dermatol., 74, 13-16 (1980). (4) L. H. Jansen, T. Hojyo, and A.M. Kligman, Improved fluorescence staining technique for esti- mating turnover of the human stratum corneum, Brit. J. Dermatol., 90, 9-12 (1974). (5) M. Takahashi, Y. Machida, and R. Marks, A new apparatus to measure rate of desquamation using dansyl chloride fluorescence, Arch. Dermatol. Res., in press. (6) L. Rowe and W. J. Dixon, Clustering and control of mitotic activity in human epidermis, J. Invest. Dermatol., 58, 16-23 (1972).
-• J. Soc. Cosmet. Chem., 38, 333-339 (September/October 1987) Bioconversion of a provitamin to vitamins C and E in skin KAKUJI TOJO and AE-RI C. LEE, Department of Pharmaceutics, William Levine Hall of College of Pharmacy, Rutgers--The State University of New Jersey, Busch Campus, Piscataway, NJ 08855-0789. Received May 4, 1987. Synopsis Skin bioconversion of a new provitamin, dl-o•-tocopherol-L-ascorbic acid sodium phosphate diester, for vitamins C and E, was investigated using a hairless mouse skin in vitro. The provitamin, which is quite stable in aqueous solutions, was efficiently bioconverted to both vitamins in the viable skin of hairless mice. The appearance rate of vitamin C, after the provitamin bioconversion, reached a steady state very quickly and virtually no time lag was observed. The appearance rate of vitamin E, after the bioconversion, increased gradually during the entire period of the permeation and bioconversion experiment (72 hours), after a long time lag (about 24 hours). The long time lag indicates that vitamin E may bind strongly to the skin tissue. From the steady-state appearance rates of vitmin C and the provitamin, the yield of the skin bioconversion was found to be 96% in the hairless mouse skin. INTRODUCTION Ascorbic acid (vitamin C) and o•-tocopherol (vitamin E) are two essential vitamins. An adequate supply of these vitamins is needed to preserve healthy skin as well as to avoid various deficiency diseases (1). Vitamin C plays an important role in several oxidation reactions. It is believed that this vitamin is essential for hydroxylation of prolyl and lysyl residues in growing chains of hydroxylareal procollagen peptide in the skin (2). Vitamin E, on the other hand, has been applied topically for many years as a natural moisturizer. In recent studies, various therapeutic efficacies of vitamin E have been revealed (3,4). Vitamins C and E were found to function in a synergistic fashion to protect against the peroxidation of membrane lipids (5,6). Vitamin E is a lipophilic compound (octanol/water partition coefficient = 480), while vitamin C is a hydrophilic compound (partition coefficient = 0.02) which is hardly soluble in lipophilic solu- tions. Vitamins C and E are not stable in many solutions (1,7), although the stability may be enhanced by using various stabilizing agents (8). Since the skin is a highly heterogeneous membrane which consists of lipophilic stratum comeurn and lipophobic viable skin, the skin permeation of a drug depends on the hydrophilicity or lipophilicity of the penerrant. In recent years, the percutaneous absorption of various drugs has been studied exten- sively to develop either topical or systemic drug delivery (9- 11). Topical application of 333
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