Enhancement effects of double-chained cationic surfactants of n-dimethyldialkylammoniums on permeability of salicylate through guinea pig dorsal skin.

We examined the enhancement effects of the double-chained cationic surfactants of n-dimethyldialkylammoniums (CH(3))(2)N(+)(C(n)H(2n+1))(2) on the permeation of anionic salicylate through excised guinea pig dorsal skin at pH 7.4. Among them, n-dimethyldidecylammonium (2C10), which seemed to form micelles, had dose-dependent enhancement effects at concentrations of more than 0.1 mM, and about a ninety-fold increase in the permeability coefficient of salicylate was observed at 2 mM. The enhancement effect of 2C10 was larger than those of single-chained cationic surfactants of n-alkyltrimethylammoniums. n-Dimethyldilaurylammonium (2C12), which seemed to form bilayer vesicles, induced about a twenty five-fold increase in the permeability coefficient. The enhancement effects of n-dimethyldialkylammoniums decreased with the increase in their alkyl chain lengths. In contrast, only slight stimulation by these cationic surfactants was observed for silicon rubber membrane permeation of salicylate. Analysis of the retention of the salicylate in the skin suggested that the double-chained cationic surfactants-induced increase in the transfer of salicylate to the skin is the main reason for the marked stimulation of the skin permeation.