title: A Multiscale Study on the Penetration Enhancement Mechanism of Menthol to Osthole.
abstract: Menthol is a widely used penetration enhancer in clinical medicine due to its high efficiency and relative safety. However, details of the penetration enhancement mechanism of menthol on the molecular level is rarely involved in the discussion. In this work, the penetration enhancement (PE) mechanism of menthol is explored by a multiscale method containing molecular dynamics simulations, in vitro penetration experiments, and transmission electron microscopy. Osthole is chosen to be the tested drug due to its common use in external preparations and because it often accompanies menthol as a PE in the preparations. The results show that menthol in each testing concentration can impair the lipid packing of stratum corneum (SC) and promote osthole permeating into SC, and the penetration promoting effect has an optimal concentration. At a low concentration, menthol causes the bilayer to relax with a reduction in thickness and increment in the lipid headgroup area. At a high concentration, menthol destroys the bilayer structure of SC and causes lipids to form a reversed micelle structure. The penetration enhancement mechanism of menthol is characterized mainly by the disruption of the highly ordered SC lipid in low concentrations and an improvement in the partitioning of drugs into the SC in high concentrations. The results can provide some assistance for additional studies and applications of menthol as a penetration enhancer.
authors: Beijing University of Chinese Medicine , Beijing 100102, China.|Key Laboratory of TCM-information Engineer of State Administration of TCM, Beijing 100102, China.
authors: Shufang
authors: S
authors: Yang
authors: School of Traditional Chinese Medicine, Capital Medical University , Beijing 100069, China.
authors: Ran
authors: R
authors: Wang
authors: Beijing University of Chinese Medicine , Beijing 100102, China.|School of Traditional Chinese Medicine, Capital Medical University , Beijing 100069, China.
authors: Guang
authors: G
authors: Wan
authors: Beijing University of Chinese Medicine , Beijing 100102, China.|Key Laboratory of TCM-information Engineer of State Administration of TCM, Beijing 100102, China.
authors: Zhimin
authors: Z
authors: Wu
authors: Beijing University of Chinese Medicine , Beijing 100102, China.
authors: Shujuan
authors: S
authors: Guo
authors: Beijing University of Chinese Medicine , Beijing 100102, China.|Key Laboratory of TCM-information Engineer of State Administration of TCM, Beijing 100102, China.
authors: Xingxing
authors: X
authors: Dai
authors: Beijing University of Chinese Medicine , Beijing 100102, China.|Key Laboratory of TCM-information Engineer of State Administration of TCM, Beijing 100102, China.
authors: Xinyuan
authors: X
authors: Shi
authors: Beijing University of Chinese Medicine , Beijing 100102, China.|Key Laboratory of TCM-information Engineer of State Administration of TCM, Beijing 100102, China.
authors: Yanjiang
authors: Y
authors: Qiao
mesh_terms: D002462:Cell Membrane / Q000378:metabolism; D003374:Coumarins / Q000737:chemistry / Q000378:metabolism*; D004058:Diffusion; D004817:Epidermis / Q000378:metabolism; D008051:Lipid Bilayers / Q000378:metabolism; D008610:Menthol / Q000737:chemistry / Q000378:metabolism*; D008968:Molecular Conformation; D056004:Molecular Dynamics Simulation; D010539:Permeability; D012869:Skin Absorption
chemical_list: D003374:Coumarins; D008051:Lipid Bilayers; D008610:Menthol; C046627:osthol