Application of Molecular Dynamics Simulation To Predict the Compatability between Water-Insoluble Drugs and Self-Associating Poly(ethylene oxide)-b-poly(ε-caprolactone) Block Copolymers
Application of Molecular Dynamics Simulation To Predict the Compatability between Water-Insoluble Drugs and Self-Associating Poly(ethylene oxide)-b-poly(ε-caprolactone) Block Copolymers
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DOI：
10.1021/bm800320z
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发表时间：
2008-11-01
影响因子：
6.2
通讯作者：
Choi, Phillip
中科院分区：
文献类型：
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作者：
Patel, Sarthak;Lavasanifar, Afsaneh;Choi, Phillip
本工作采用分子动力学(MD)模拟方法研究了非诺贝特和尼莫地平两种水不溶性药物在不同相对分子质量嵌段组合形成胶束的PEO-b-PCL嵌段共聚物中的溶解度。然后将基于MD结果的溶解度预测结果与溶解度实验和常用的基团贡献法(GCM)进行了比较。结果表明，分子动力学模拟计算的Flory-Huggins相互作用参数与药物/PEO-b-PCL体系的溶解度数据基本一致，而GCM计算的结果与实验结果有较大偏差。我们还考虑了药物在PEO-b-PCL的PEO嵌段中增溶的可能性。
In the present work, molecular dynamics (MD) simulation was applied to study the solubility of two water-insoluble drugs, fenofibrate and nimodipine, in a series of micelle-forming PEO-b-PCL block copolymers with combinations of blocks having different molecular weights. The solubility predictions based on the MD results were then compared with those obtained from solubility experiments and by the commonly used group contribution method (GCM). The results showed that Flory-Huggins interaction parameters computed by the MD simulations are consistent with the solubility data of the drug/PEO-b-PCL systems, whereas those calculated by the GCM significantly deviate from the experimental observation. We have also accounted for the possibility of drug solubilization in the PEO block of PEO-b-PCL.