通过实验和计算方法分析基于β-乳糖球蛋白的无形固体分散中的稳定机制
Xuezhi Zhuo1, Vito Foderà1, Per Larsson2
1Department of Pharmacy, University of Copenhagen, Copenhagen 2100, Denmark.
概括
具有高药物负载的无形固体分散 (ASD) 可以通过蛋白相互作用和键稳定. 这项研究揭示了通过各种药物分子稳定自闭症的关键机制,从而使药物度更高.
科学领域:
- 制药科学 制药科学
- 材料科学 材料科学 材料科学
- 计算化学计算化学
背景情况:
- 稳定型无形固体分散体 (ASD) 的β-乳糖球蛋白 (β-乳糖球蛋白) 显示出长期稳定性,归因于键网络.
- 了解稳定机制对于发展具有增强药物负载和生物可用性的ASD至关重要.
研究的目的:
- 用实验和计算方法研究ASD与各种药物分子的稳定机制.
- 为了确定最大的稳定药物负载的ASDs配方与furosemide,灰色,布洛芬,可纳,和rifaximin.
主要方法:
- 使用差分扫描热度计 (DSC) 和X射线粉末衍射 (XRPD) 进行实验分析.
- 采用分子动力学 (MD) 模拟来分析药物分子的扩散性和键形成.
- 在ASD模型中研究了晶体模式.
主要成果:
- 基托可纳和利法西明的ASD在90%的药物负载下保持稳定,而罗西米德,灰色富尔文和布洛芬的最大稳定负载分别为70%,50%和40%.
- 在低药物负载 (≤40%) 时,绝缘封闭和蛋白质键是关键.
- 药物间的键,离子相互作用和高的药物玻璃过渡温度 (Tg) 在较高的药物负载 (>40%) 上稳定了ASD.
结论:
- 分子动力学模拟可以有效预测ASD稳定性.
- 多种稳定机制,包括蛋白-药物和药物-药物相互作用,在不同的药物负载下促进ASD稳定性.
- 这项研究提供了关于优化ASD配方以改善药物输送的见解.
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