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Permeation‐enhancing effects and mechanisms of borneol and menthol on ligustrazine: A multiscale study using in vitro and coarse‐grained molecular dynamics simulation methods
Author(s) -
Dai Xingxing,
Wang Ran,
Wu Zhimin,
Guo Shujuan,
Yang Chang,
Ma Lina,
Chen Liping,
Shi Xinyuan,
Qiao Yanjiang
Publication year - 2018
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/cbdd.13350
Subject(s) - permeation , borneol , transdermal , stratum corneum , chemistry , menthol , molecular dynamics , drug , lipid bilayer , emulsion , bilayer , passive transport , pharmacology , biophysics , chromatography , membrane , organic chemistry , computational chemistry , biochemistry , medicine , alternative medicine , traditional chinese medicine , pathology , biology
Borneol ( BO ) and menthol ( MEN ) are two widely used natural permeation enhancers in the transdermal drug delivery system. In previous studies, their permeation enhancement effects and mechanisms of action on the hydrophobic drug osthole (logP = 3.8) and hydrophilic drug 5‐fluorouracil (logP = −0.9) have been studied. In this study, ligustrazine ( LTZ ), whose logP is 1.3, was used as a model drug to provide a comprehensive understanding of the influence of its logP on the permeation‐enhancing effects of BO and MEN . Both BO and MEN enhanced the permeation of LTZ through the skin stratum corneum, as determined using the modified Franz diffusion cell experiment. The enhancement mechanisms were illustrated by coarse‐grained molecular dynamics simulations as follows: at low concentrations, the enhancing ratio of MEN was higher than that of BO because of the stronger perturbation effects of MEN on the lipid bilayer, making it looser and facilitating LTZ diffusion. However, at high concentrations, in addition to the diffusion mechanism, BO induced the formation of water channels to improve the permeation of LTZ ; however, MEN had no significant effects through this mechanism. Their results were different from those found with osthole and 5‐fluorouracil and have been discussed in this study.