Comparison of the Effects of Chemical Permeation Enhancers on the Lipoidal Pathways of Human Epidermal Membrane and Hairless Mouse Skin and The Mechanism of Enhancer Action

• Published in: Journal of pharmaceutical sciences Vol. 96; no. 9; pp. 2310 - 2326
• Main Authors: Chantasart, Doungdaw, Sa‐Nguandeekul, Piyanuch, Prakongpan, Sompol, Li, S.Kevin, Higuchi, William I.
• Format: Journal Article
• Language: English
• Published: Hoboken Elsevier Inc 01.09.2007; Wiley Subscription Services, Inc., A Wiley Company; Wiley; American Pharmaceutical Association
• Subjects: Adult; Aged; Algorithms; Animals; Biological and medical sciences; Cell Membrane - chemistry; chemical permeation enhancers; Chemical Phenomena; Chemistry, Physical; Chromatography, Gas; Corticosterone - administration & dosage; Corticosterone - chemistry; Electric Impedance; Epidermis - cytology; Estradiol - metabolism; Excipients; Female; General pharmacology; hairless mouse skin; human epidermal membrane; Humans; In Vitro Techniques; Lipids - chemistry; Medical sciences; Mice; Mice, Hairless; Middle Aged; Permeability; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Skin Absorption - drug effects; Solubility; hairless mouse skin; chemical permeation enhancers; human epidermal membrane; Human; Pharmaceutical technology; Rodentia; Epidermis; Vertebrata; Mammalia; Mouse; Animal; Membrane; Skin; Absorption enhancer; Mechanism of action; Comparative study
• ISSN: 0022-3549; 1520-6017
• DOI: 10.1002/jps.20865

Previously, the effects of chemical permeation enhancers upon the permeability of the lipoidal pathway of hairless mouse skin (HMS) were investigated and a quantitative structure enhancement relationship was established. The present study was to study the effects of these enhancers on human epidermal membrane (HEM) using the same experimental method employed in the previous HMS studies. The effects of enhancers on the permeability coefficients of the lipoidal pathways of HEM and HMS for corticosterone were found to be essentially the same. In the equilibrium uptake studies of the enhancers and β‐estradiol, it was found that the amounts of enhancers taken up and the partitioning of β‐estradiol into the HEM stratum corneum (SC) intercellular lipid under the E = 10 conditions were different from those of HMS. Despite these differences, the HEM data show a correlation between the intercellular lipid/PBS partition coefficients of the enhancers and the enhancer n‐octanol/PBS partition coefficients. This correlation is consistent with the observed chemical microenvironment of the site of enhancer action in the HMS SC in previous studies. Therefore, provided with proper experimental protocols, HMS can be a reliable model for the evaluation of the effects of skin permeation enhancers on the lipoidal pathway of HEM. © 2007 Wiley‐Liss, Inc. and the American Pharmacists Association J Pharm Sci 96: 2310–2326, 2007