Spin Lapel Study on the Enhancement Mechanism of Transdermal Absorption Enhancers

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We examined characteristics of enhancement effects of various compounds on transdermal drug absorption. Among various compounds n-alkyltrimethylammoniums showed marked enhancement effects on relatively hydrophilic drugs. From the analysis of the free energy of transfer of the methylene group of the 4-alkyl substituents of benzoic acid from the aqueous phase to skin on their permeability data, it was suggested that the cationic surfactants made the skin relatively more hydrophilic. To obtain the information on the localization of alkyl compounds in the skin, the electron spin resonance spectra of alkyl spin labels were observed in the excised guinea pig dorsal skin, its stratum corneum, delipidized skin and stratum corneum model lipid liposomes. According to the analysis fatty acid spin label seemed to be present in the stratum corneum rigid lipid lamella, fatty acid ester spin label in the relatively fluid environment. On the other hand, long-chain cationic spin label seemed to be present in the protein region of the stratum corneum. The latter finding suggested that the interaction of the cationic surfactants with the proteins was the reason for their significant enhancement effects. These findings indicated that the different interaction and different localization of the alkyl compounds depended on their electronic charge as well as their alkyl chain lengths. We furthermore studied the molecular assemblies of double-chained cationic surfactants by spin label study and revealed their enhancement mechanism on transdermal drug absorption.