文献类型：期刊文献

英文题名：Unraveling the Molecular Mechanisms of Alcohol-Mediated Skin Permeation Enhancement: Insights from Molecular Dynamics Simulations

作者：Cheng, Shiqiang[1]; Zhou, Kangfu[2]; Wang, Feifei[2,3]; Ye, Zhicheng[1]; Ye, Chuanjun[2]; Lian, Cheng[1]; Shang, Yazhuo[1]; Liu, Honglai[1]

机构：[1] Key Laboratory for Advanced Materials, School of Chemistry and Molecular Engineering, East China University of Science and Technology, Shanghai, 200237, China; [2] Yunnan Botanee Bio-technology Group Co., Ltd., Yunnan, 650106, China; [3] Yunnan Yunke Characteristic Plant Extraction Laboratory Co., Ltd., Yunnan, 650106, China

年份：2024

卷号：40

期号：1

起止页码：594

外文期刊名：Langmuir

收录：EI(收录号：20240115316178)

语种：英文

外文关键词：Defects - Drug delivery - Ethanol - Extraction - Fatty acids - Free energy - Hydrophilicity - Lipid bilayers - Lipids - Molecular dynamics - Molecules - Permeation

摘要：The application of alcohols as permeation enhancers in pharmaceutical and cosmetic formulations has attracted considerable attention, owing to their skin permeation-enhancing effect. Nonetheless, the elucidation of the fundamental mechanisms underlying the skin permeation-enhancing effect remains elusive. In this study, molecular dynamics (MD) simulations were employed to investigate the effect of 1,2-propanediol (1,2-PDO), 1,2-butanediol (1,2-BDO), and ethanol (EtOH) on the stratum corneum (SC) model membrane. The results showed that the effect of alcohols on the SC model membrane displayed a concentration-dependent nature. The alcohols can interact with SC lipids and exhibit a remarkable ability to selectively extract free fatty acid (FFA) molecules from the SC model membrane and make the SC looser. Meanwhile, 1,2-BDO and EtOH can penetrate into SC lipid bilayers at higher concentrations, leading to the formation of continuous hydrophilic defects in SC. The FFA extraction and the formation of continuous hydrophilic defects induced ceramide (CER) tail chains to become more disordered and fluid and also weakened the hydrogen bonding (H-bonding) network among SC lipids. Both the FFA extraction and the continuous hydrophilic defect formation endowed alcohols with the permeation-enhancing effect. The constrained simulations revealed that the free energy barriers decreased for the permeation of the hydrophilic model molecule (COL) across the SC model membranes containing alcohols, particularly for 1,2-BDO and EtOH. The possible permeation-enhancing mechanisms of alcohols were proposed correspondingly. This work not only provided a deep understanding of the transdermal permeation-enhancing behavior of alcohols at the molecular level but also provided necessary reference information for designing effective transdermal drug delivery systems in applications. ? 2023 American Chemical Society.