Abstract
Permeation of the model hydrophilic compound 5-fluorouracil was studied through human epidermal membranes treated with penetration enhancers oleic acid in propylene glycol, d-limonene, 1,8-cineole, menthone and nerolidol for times ranging from 1 to 12 h. Partitioning of the drug from aqueous solutions into enhancer treated human stratum corneum was also measured. Differential scanning calorimetry probed the mechanisms of action of these enhancers. All five substances increased the permeation of 5-fluorouracil, probably mainly by disrupting the intercellular lipid lamellar structure. The enhancement effects of d-limonene and oleic acid were saturable within 6 h, reaching a limiting value of about 3.6- and 24-fold increase in drug flux, respectively, whereas 1,8-cineole, menthone and nerolidol showed increasing effects with time leading to maximum enhancements of about 95-, 42- and 25-fold increase, respectively, after 12 h, probably related to improved drug partitioning. Lipid extraction was negligible.
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