水溶液
化学
生物利用度
紫杉醇
分子
胶束
分子动力学
吸收(声学)
药品
氢键
疏水效应
生物物理学
有机化学
计算化学
材料科学
癌症
药理学
内科学
复合材料
生物
医学
出处
期刊:Current Drug Delivery
[Bentham Science]
日期:2019-10-03
卷期号:16 (7): 618-627
被引量:11
标识
DOI:10.2174/1567201816666190313155117
摘要
Background: Glycyrrhizic acid (GA) is a glycoside that has shown considerable promise as a penetration enhancer and drug carrier to improve the absorption of poorly water-soluble drugs. The aggregation behavior of GA and its ability to form large micelles at higher solution concentrations are thought to contribute to these bioavailability enhancing properties. The oral absorption of Paclitaxel (PTX) for example, an anti-cancer agent which exhibits poor oral bioavailability, has been found to significantly increase in the presence of GA. Methods: In an attempt to visualize the aggregation behavior of GA and its subsequent association with PTX, 100 ns molecular dynamics simulation of a 5 mM aqueous solution of GA with 10 molecules of PTX was conducted using GROMACS and an all-atom forcefield. Results: Aggregation of GA molecules was found to occur quickly at this level of saturation leading to two stable aggregates of 13 and 17 GA molecules with an effective radius of 10.17 nm to 10.92 nm. These aggregates form not in isolation, but together with PTX molecule embedded within the structures, which reduces the number of interactions and hydrogen-bonding with water. Conclusion: GA aggregation occurs around PTX molecules in solution, forming co-joined GA-PTX cluster units at a ratio of 3:1. These clusters remain stable for the remainder of the 100ns simulation and serve to isolate and protect PTX from the aqueous environment.
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