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We investigated the usefulness of a liposome composed of lipid components of stratum corneum as a system to evaluate the enhancing ability of various penetration enhancers. Changes in the lipid fluidity of the model lipid liposome membrane, consisting of ceramide (40%), cholesterol (25%), palmitic acid (25%) and cholesterol 3-sulfate (10%), by the addition of 1-dodecylazacycloheptan-2-one (Azone), oleic acid (OA) or dimethyl sulfoxide (DMSO) were measured by a fluorescence polarization method using 1,6-diphenyl-1,3,5-hexatriene, dansylhexadecylamine and cholesteryl anthracene-9-carboxylate as probes for the hydrophobic lipid, the polar head and cholesterol regions of the lipid bilayer, respectively. The order of lipid fluidizing ability was suggested to be Azone &gt; OA &gt; DMSO. An in vitro permeation study of six beta-blocking agents, propranolol, metoprolol, timolol, pindolol, nadolol and atenolol, was carried out to estimate the enhancing effect of the enhancers using rat abdominal skin. Azone showed a strong facilitating effect on the drug permeation and the effect of OA was weaker than that of Azone. DMSO showed little effect unless a high concentration of over 60% (w/v) was employed. The basis for these enhancing mechanisms is the change in diffusion constant of a drug in the rat skin. These results were consistent with those obtained from the lipid fluidity measurement, that is to say, the stronger the increment effect of the enhancer on the fluidity of the model lipid liposome is, the larger is the D value for the drug in the skin. Applicability of the model lipid liposome in evaluating the penetration enhancer was thus demonstrated.

biological and pharmaceutical bulletin

Keratinized Epithelial Transport of .BETA.-Blocking Agents. III. Evaluation of Enhancing Effect on Percutaneous Absorption Using Model Lipid Liposomes.