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- W1531629788 abstract "We investigated the effects of the nonionic surfactant, n-decylmethyl sulfoxide (NDMS), pH, and inhibitors on the metabolism and the permeation of amino acids, dipeptides, and the pentapeptide enkephalin, through hairless mouse skin. An HPLC gradient method was developed to identify the possible peptide and amino acid metabolites of leucine-enkephalin. NDMS increased the permeability of all amino acids and peptides tested. At neural pH, the enzyme activity within the skin was such that no flux of leucine-enkephalin (YGGFL) was observed and the donor cell concentration of YGGFL decreased rapidly. The major cleavage occurred at the Tyr-Gly bond. At pH 5.0 the metabolic activity was reduced significantly and a substantial flux of YGGFL was observed. Enzymatically stable YGGFL analogues, Tyr-D-Ala-Gly-Phe-Leu (YDAGFL) and its amide, exhibited significant fluxes even at neutral pH in the presence of NDMS, but with substantial metabolism. YDAGFL amide was more stable to metabolism than YDAGFL. The rates of metabolism of the peptides in the skin homogenates were in the order: FL.>>YGGFL > GFL > GGFL >> YG, YGG >> YDAGFL amide. In the skin homogenates puromycin and amastatin showed the highest inhibitory effects, while FL and GFL were only slightly active. However, in the skin diffusion experiments, FL allowed the highest amount of intact parent compound to permeate, making it the most potent inhibitor. These results show that the complex proteolytic enzyme activities occurring during skin permeation are different from those in skin homogenates and that a combination of enhancer, pH adjustment, and inhibitors can increase the transdermal delivery of peptides." @default.
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- W1531629788 date "1990-01-01" @default.
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- W1531629788 doi "https://doi.org/10.1023/a:1015915922363" @default.
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