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 logK_o/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.

• Fourier transform infrared spectroscopy
• menthone
• molecular dynamic simulation
• penetration enhancer
• stratum corneum
• transdermal delivery

Acknowledgements

The authors thank Dr. Yanling Zhang (School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China) for her assistance in Molecular dynamic simulation.

Declaration of interest

The authors report no declarations of interest.

This project is supported by National Natural Science Foundation of China (no. 81473365) and Innovative Research Team in Beijing University of Chinese Medicine (no. 2011-CXTD-13).