通过基于循环二烯的纳入复杂化来提高索拉费尼布的溶解性和稳定性:in silico和in vitro研究
Aamir Aman1, Saba Ali2, Panupong Mahalapbutr3
1Program in Bioinformatics and Computational Biology, Graduate School, Chulalongkorn University Bangkok 10330 Thailand t.rungrotmongkol@gmail.com.
RSC advances
|September 13, 2023
概括
由于溶解性差,索拉费尼布的生物可用性较低. 修改后的环氧素,特别是硫乙-β-环氧素 (SBEβCD),有效地与索拉费尼布形成包容复合物,增强其溶解性和稳定性.
科学领域:
- 药理学 药理学是指药理学的学科.
- 物理化学 物理化学
- 计算化学计算化学
背景情况:
- 索拉菲尼布 (SOR) 是一种口服的多酶抑制剂,对癌症治疗至关重要.
- 由于SOR的口服生物可用性有限,这归因于其水溶性差.
- 循环德克斯 (CDs) 被探索以提高像SOR.这样的脂性药物的可溶性和稳定性.
研究的目的:
- 调查各种循环素 (βCD衍生物和γCD) 在与索拉芬尼布 (SOR) 形成包容复合物的潜力.
- 用计算和实验方法评估SOR-CD复合物的结合亲和力和稳定性.
- 为了确定最有效的循环德克斯来增强SOR的药物特性.
主要方法:
- 分子动力学模拟 (200 ns) 来分析SOR-CD复合体的形成和相互作用.
- 使用SIE,MM/GBSA和MM/PBSA方法计算结合亲缘关系.
- 在25°C时实验确定SOR-CD复合物的稳定常数.
主要成果:
- 索拉费尼布与所有测试的环极在两个方向 (P型和C型) 中形成了包含复合体,由范德瓦尔斯力驱动.
- 硫乙-β-环德 (SBEβCD) 显示了与SOR.的最高原子接触和最低溶剂可访问性.
- 与βCD (210 M-1) 相比,SBEβCD表现出最高的结合亲和力和显著更高的稳定常数 (940 M-1).
结论:
- 修改后的环素,特别是SBEβCD,是Sorafenib的有效分子封装剂.
- SBEβCD显示了提高Sorafenib的可溶性和稳定性的显著潜力.
- 这些发现支持对像Sorafenib这样的脂性药物进行增强的药物递送系统的开发.
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