Effect of linolenic acid/ethanol or limonene/ethanol and iontophoresis on the in vitro percutaneous absorption of LHRH and ultrastructure of human epidermis.
The effect of enhancer(s) (e.g. ethanol (EtOH), 5% linolenic acid/EtOH, and 5% limonene/EtOH) and iontophoresis was investigated on the in vitro percutaneous absorption of luteinizing hormone releasing hormone (LHRH) and ultrastructure of human epidermis by transmission electron microscopy (TEM). 5% linolenic acid/EtOH or 5% limonene/EtOH significantly enhanced (P<0.05) the passive flux of LHRH through human epidermis in comparison to the control (no enhancer treated epidermis). Iontophoresis further increased the flux of LHRH through enhancer(s) treated epidermis. Iontophoretic flux of LHRH through 5% linolenic acid/EtOH and 5% limonene/EtOH treated epidermis was significantly (P<0.05) enhanced in comparison to iontophoretic flux through the control epidermis. TEM is the most efficient way to visualize the ultrastructure of the stratum corneum (SC). TEM results reveal that iontophoresis in combination with enhancers (e.g. linolenic acid/EtOH or and limonene/EtOH) transformed the highly compact cells of the SC into a looser network of filaments, disrupted the keratin pattern, and resulted in swelling of SC cell layers of human epidermis. Thus, linolenic acid/EtOH or limonene/EtOH in combination with iontophoresis increased the flux of LHRH through human epidermis by disrupting keratin pattern as well as loosening and swelling of SC cell layers.
Bhatia
K S
KS
Department of Pharmaceutical Sciences, College of Pharmacy, North Dakota State University, Fargo, ND 58105, USA.
Singh
J
J
D053138:Cyclohexenes; D004817:Epidermis / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure*; D000431:Ethanol / Q000494:pharmacology*; D018757:GABA Modulators / Q000493:pharmacokinetics; D007987:Gonadotropin-Releasing Hormone / Q000493:pharmacokinetics*; D006801:Humans; D066298:In Vitro Techniques; D007478:Iontophoresis; D000077222:Limonene; D008854:Microscopy, Electron; D010592:Pharmaceutic Aids / Q000494:pharmacology; D012869:Skin Absorption / Q000187:drug effects*; D013729:Terpenes / Q000494:pharmacology*; D017962:alpha-Linolenic Acid / Q000494:pharmacology*
D053138:Cyclohexenes; D018757:GABA Modulators; D010592:Pharmaceutic Aids; D013729:Terpenes; D017962:alpha-Linolenic Acid; D007987:Gonadotropin-Releasing Hormone; D000431:Ethanol; D000077222:Limonene