title: Effect of menthone and related compounds on skin permeation of drugs with different lipophilicity and molecular organization of stratum corneum lipids.
abstract: The objective of this article was to investigate the enhancing effect of menthone, menthol and pulegone on the transdermal absorption of drugs with different lipophilicity and probe their mechanisms of action at molecular level. Five model drugs, namely osthole, tetramethylpyrazine, ferulic acid, puerarin and geniposide, which were selected based on their lipophilicity denoted by logKo/w, were tested using in vitro permeation studies in which Franz diffusion cells and rat skin were employed. Infrared spectroscopy and molecular dynamic simulation were used to investigate the effect of these enhancers on the stratum corneum (SC) lipids, respectively. Three compounds could effectively promote the transdermal absorption of drugs with different lipophilicity, and the overall promoting capacities were in the following increasing order: pulegone < menthol < menthone. The penetration enhancement ratio was roughly in parabolic curve relationships with the drug lipophilicity after treatment with menthol or menthone, while the penetration enhancement effect of pulegone hardly changed with the alteration of the drug lipophilicity. The molecular mechanism studies suggested that menthone and menthol enhanced the skin permeability by disordering the ordered organization of SC lipids and extracted part of SC lipids, while pulegone appeared to promote drug transport across the skin only by extracting part of SC lipids.
authors: a Department of TCM Pharmaceutics , School of Chinese Materia Medica, Beijing University of Chinese Medicine , Beijing , China.
authors: Yi
authors: Y
authors: Lan
authors: a Department of TCM Pharmaceutics , School of Chinese Materia Medica, Beijing University of Chinese Medicine , Beijing , China.
authors: Jingyan
authors: J
authors: Wang
authors: a Department of TCM Pharmaceutics , School of Chinese Materia Medica, Beijing University of Chinese Medicine , Beijing , China.
authors: Hui
authors: H
authors: Li
authors: a Department of TCM Pharmaceutics , School of Chinese Materia Medica, Beijing University of Chinese Medicine , Beijing , China.
authors: Yewen
authors: Y
authors: Zhang
authors: a Department of TCM Pharmaceutics , School of Chinese Materia Medica, Beijing University of Chinese Medicine , Beijing , China.
authors: Yanyan
authors: Y
authors: Chen
authors: a Department of TCM Pharmaceutics , School of Chinese Materia Medica, Beijing University of Chinese Medicine , Beijing , China.
authors: Bochen
authors: B
authors: Zhao
authors: a Department of TCM Pharmaceutics , School of Chinese Materia Medica, Beijing University of Chinese Medicine , Beijing , China.
authors: Qing
authors: Q
authors: Wu
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D050356:Lipid Metabolism / Q000187:drug effects; D008055:Lipids / Q000737:chemistry; D008297:Male; D008610:Menthol / Q000494:pharmacology*; D056004:Molecular Dynamics Simulation; D004364:Pharmaceutical Preparations / Q000008:administration & dosage* / Q000737:chemistry; D014677:Pharmaceutical Vehicles / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012867:Skin / Q000187:drug effects* / Q000378:metabolism; D012869:Skin Absorption / Q000187:drug effects*
chemical_list: D008055:Lipids; D004364:Pharmaceutical Preparations; D014677:Pharmaceutical Vehicles; D008610:Menthol; C019466:menthone
keywords: Fourier transform infrared spectroscopy; menthone; molecular dynamic simulation; penetration enhancer; stratum corneum; transdermal delivery