Vitamin E acts as an antioxidant and protects molecules, especially polyunsaturated fats, against attack with free-radicals and the initiation of peroxidation.1,2) It has been generally accepted that vitamin E plays an important role in the stabilization of biological membranes that contain high levels of polyunsaturated fatty acids. [3][4][5] Therefore without sufficient amounts of vitamin E, the arrangement of the hydrocarbon regions of biological membranes become disordered and oxidative destruction of the polyunsaturated fatty acids may be facilitated. The effect of vitamin E on the skin permeability is more significant when the phospholipid contains a higher content of arachidonic acid residues. Vitamin E forms a complex with the phospholipids having arachidonyl residues that are present in cellular membranes. Diplock and Lucy reported that a-tocopherol could reduce the permeability to glucose and chromate ions when the liposome consisted of phospholipids containing arachidonic acid residues. 6,7) In studies to understand the role of vitamin E in our body, many researches have stressed the structural link between vitamin E and phospholipids in cellular membranes.For most drugs, after removing the donor solution after achieving a steady state of permeation rate, the profile shows an increase in skin permeation rate due to some reservoir capacity of the skin. 7-9) Miselinicky 10) reported that materials with good lipid solubility or a high affinity for protein would be retained within the skin structure to the greatest extent since increasing lipophilicity and protein binding promote reservoir formation. However, vitamin E which is a very lipophilic compound (partition coefficient, octanol/water: 437) did not show any increase after desorption study indicating no reservoir formation or very strong chemical binding which can not be explained by simple Langmuir-type binding. 9,11) To determine the amount of vitamin E which attends in the diffusion process (the free diffusable drug concentration), skin permeation studies with whole skin and stripped skin were performed. From the lag times and the steady state skin permeation rates, the drug solubility, diffusivity and partition coefficient in each skin layer were determined by employing a bi-layer model. 12) From our previous experiments, it was shown that vitamin E metabolized into a-tocopherol quinone and a-tocopherol quinol in hairless mouse skin. To understand the binding property of vitamin E after topical application, tritium labeled vitamin E was employed. Tritium labeled vitamin E in the skin can be either vitamin E, a-tocopherolquinone or a-tocopherolquinol.13) Since the molecular weights of these three compounds are similiar; they differ by only one hydroxyl functional group and two hydrogen atoms respectively, a-tocopherol (C 29 H 50 O 2 ϭ430.7), a-tocopherol quinone (C 29 H 49 O 3 ϭ445.7), a-tocopherolquinol (C 29 H 51 O 3 ϭ 447.7). We investigated the binding property of vitamin E during skin permeation by employing the bi-layer model.
12)Differenti...