Interaction of menthol with mixed-lipid bilayer of stratum corneum: A coarse-grained simulation study
Guang Wan1, Xingxing Dai2, Qianqian Yin3
1School of Traditional Chinese Medicine, Capital Medical University, Beijing 100069, China; Beijing University of Chinese Medicine, Beijing 100102, China.
Abstract:
Menthol is a widely used penetration enhancer in clinical medicine due to its high efficiency and relative safety. Although there are many studies focused on the penetration-enhancing activity of menthol, the details of molecular mechanism are rarely involved in the discussion. In this study, we present a series of coarse-grained molecular dynamics simulations to investigate the interaction of menthol with a mixed-lipid bilayer model consisting of ceramides, cholesterol and free fatty acids in a 2:2:1 molar ratio. Taking both the concentration of menthol and temperature into consideration, it was found that a rise in temperature and concentration within a specific range (1-20%) could improve the penetration-enhancing property of menthol and the floppiness of the bilayer. However, at high concentrations (30% and more), menthol completely mixed with the lipids and the membrane can no longer maintain a bilayer structure. Our results elucidates some of the molecular basis for menthol's penetration enhancing effects and may provide some assistance for the development and applications of menthol as a penetration enhancer. Furthermore, we establish a method to investigate the penetration enhancement mechanism of traditional Chinese medicine using the mixed-lipid bilayer model of stratum corneum by molecular dynamics simulations.
Insights
Menthol enhances skin penetration by increasing lipid bilayer fluidity at specific concentrations (1-20%). Higher concentrations disrupt membrane structure, revealing menthol
Area of Science:
- Biophysics
- Materials Science
- Pharmacology
Background:
- Menthol is a common penetration enhancer in medicine.
- Its molecular mechanism of action is not fully understood.
- Existing research focuses on its efficacy, not underlying interactions.
Purpose of the Study:
- Investigate menthol's interaction with a lipid bilayer model.
- Elucidate the molecular basis of menthol's penetration-enhancing effects.
- Establish a simulation method for traditional Chinese medicine penetration enhancers.
Main Methods:
- Coarse-grained molecular dynamics simulations.
- Utilized a mixed-lipid bilayer model (ceramides, cholesterol, fatty acids).
- Varied menthol concentration (1-30%+) and temperature.
Main Results:
- Increased temperature and menthol concentration (1-20%) enhanced penetration and bilayer fluidity.
- High menthol concentrations (30%+) disrupted the bilayer structure.
- Identified specific concentration and temperature ranges for optimal enhancement.
Conclusions:
- Results elucidate the molecular mechanism of menthol's penetration enhancement.
- Findings support menthol's application as a penetration enhancer.
- The simulation method can be applied to study other traditional Chinese medicine enhancers.
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