Effects of skin metabolism on percutaneous penetration of drugs with high lipophilicity were studied in vitro using rat skin pretreated with and without an esterase inhibitor, diisopropyl phosphorofluoridate [also known as diisopropyl fluorophosphate (DFP)]. Without DFP, about 96% of the total penetrated amount appeared as metabolized p-hydroxybenzoic acid in the receptor fluid after application of butylparaben, whereas about 30% penetrated as intact form after application of propylparaben. On the other hand, metabolized p-hydroxybenzoic acid was not defected in the receptor fluid under pretreatment with DFP. DFP significantly decreased (p < 0.05) the total amount that penetrated after application of butylparaben, but it did not significantly affect that of propylparaben. The results indicate that skin metabolism directly affects total amount that penetrated in the case of highly lipophilic drugs, and it was found that the higher metabolic rate to hydrophilic drugs is, the greater the amount that penetrated the skin would be. Thus, when optimal prodrugs are designed for the purpose of enhancing percutaneous penetration, we propose that the bioconversion rate to parent drugs as well as the lipophilicity of prodrugs becomes an important consideration.

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IntroductionThe objective of this study is to evaluate the survival and glucose-induced insulin secretion of rat-derived insulinoma cells (INS-1) from their aggregates incorporating different size of gelatin hydrogel microspheres comparing with microspheres-free cell aggregates.MethodsThe gelatin hydrogel microspheres were prepared by the conventional w/o emulsion method. The INS-1 cells were cultured in a V-bottomed well, combining with or without the gelatin hydrogel microspheres to form their aggregates with or without microspheres.ResultsWhen the cell viability, the live cell number, the reductase activity, and the insulin secretion of cell aggregates were evaluated 7 or 14 days after incubation, the cell aggregates incorporating gelatin hydrogel microspheres showed higher cell viability, reductase activity and a larger number of live cells. The cell aggregates incorporating larger size and number of gelatin hydrogel microspheres secreted a larger amount of insulin, compared with those incorporating smaller size and number of microspheres or without microspheres.ConclusionIt is conceivable that the incorporation of gelatin hydrogel microspheres in cell aggregates is promising to improve their survival and insulin secretion function.

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