Effects of double-chained cationic surfactants n-dimethyldialkylammoniums on skin permeation of benzoic acid through excised guinea pig dorsal skin: comparison of their enhancement effects with hemolytic effects on erythrocytes.
We examined the effects of the double-chained cationic surfactants dimethyidialkylammoniums (CH3)2N+ (CnH(2n+1))2 on the permeation of benzoic acid through excised guinea pig dorsal skin. Among five dimethyldialkylammoniums tested (n=10-18), dimethyldidecylammonium (n=10) had dose-dependent enhancement effects at concentrations of more than 20 microM. Compared with the marked enhancement effects of dimethyldialkylammoniums with relatively shorter alkyl chains, those of long-chain dimethyldialkylammoniums (n=16, 18) were much less. We compared the enhancement effects of these cationic surfactants on skin permeation with their hemolytic effects on guinea pig erythrocytes. Their enhancement effects corresponded to their hemolytic activity. The findings suggest that dimethyldialkylammoniums with relatively shorter alkyl chains, which form either vesicles with looser molecular packing or micelles and appear to be present as surfactant monomers in higher ratios than those with longer alkyl chains, favor the interaction with skin. Their enhancement mechanism is possibly similar to that of single-chained cationic surfactants.
Kitagawa
S
S
Niigata College of Pharmacy, Japan. kitagawa@niigata-pharm.ac.jp
Kasamaki
M
M
Hiyama
F
F
D000465:Algorithms; D000818:Animals; D019817:Benzoic Acid / Q000008:administration & dosage / Q000493:pharmacokinetics*; D003497:Cyclic N-Oxides; D004578:Electron Spin Resonance Spectroscopy; D004912:Erythrocytes / Q000187:drug effects*; D006168:Guinea Pigs; D006461:Hemolysis / Q000187:drug effects*; D066298:In Vitro Techniques; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology*; D012869:Skin Absorption / Q000187:drug effects*; D012995:Solubility; D013113:Spin Labels; D013501:Surface-Active Agents / Q000494:pharmacology*; D014465:Ultrasonics
D003497:Cyclic N-Oxides; D000644:Quaternary Ammonium Compounds; D013113:Spin Labels; D013501:Surface-Active Agents; C005072:5-doxylstearic acid; D019817:Benzoic Acid