设计和计算表征氨酸功能化的ZIF-8作为响应pH的口服胰岛素载体
Ali Muneer Abdulrahman1, Dina Hadi Abdullah Alaqebe2, Zainab Abdullah Kareem2
1Mustansiriyah University, College of Science, Department of Chemistry, Baghdad, Iraq.
Computational biology and chemistry
|October 9, 2025
概括
氨酸修饰的ZIF-8显示为口服胰岛素输送具有前景. 计算机建模揭示了增强的胰岛素结合和药物输送应用的有利特性.
科学领域:
- 材料科学 材料科学 材料科学
- 计算化学计算化学
- 生物医学工程 生物医学工程
背景情况:
- 像胰岛素这样的生物药物的口服输送面临着由于降解和吸收不良而面临的挑战.
- 金属有机框架 (MOF) 具有作为药物输送载体的潜力,但需要改造以提高功能.
- 对ZIF-8的氨酸修饰引入了改善药物加载和释放的特定相互作用.
研究的目的:
- 通过计算评估素修饰的ZIF-8 (ZIF-8@Arg) 作为可行的口服胰岛素输送系统.
- 描述ZIF-8@Arg和胰岛素之间的分子相互作用.
- 评估ZIF-8@Arg用于口服的环境反应性和药理动力学特性.
主要方法:
- 多尺度建模:密度函数理论 (DFT),时间依赖的DFT和分子动力学 (MD) 模拟.
- 拓分析:分子中的原子 (AIM) 和非共价相互作用 (NCI).
- 在 silico 吸收,分布,新陈代谢,分泌和毒性 (ADMET) 概况.
主要成果:
- 在ZIF-8@Arg-胰岛素接口通过静电和结合增强结合稳定性.
- 在基本条件下观察到胀的pH依赖的结构适应性.
- 良好的透性 (溶解能,logP) 和预测的低毒性 (ADMET).
结论:
- 与未经修改的MOF相比,ZIF-8@Arg显示了更好的胰岛素相互作用和稳定性.
- 该材料表现出可调节释放特性和可接受的药物动力学特征,用于口服.
- ZIF-8@Arg是一个有前途的候选人,可以作为一个功能MOF的口服递送系统进行进一步的研究.
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