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关于可水解的核心交联聚合物微粒的降解的机制研究

Erik R Hebels¹, Mies J van Steenbergen¹, Ragna Haegebaert²

¹Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, 3508 TB Utrecht, The Netherlands.

Langmuir : the ACS journal of surfaces and colloids

|August 15, 2023

概括

与小型交叉连接剂相比,当使用互补聚合物进行交叉连接时,核心交叉连接聚合物微粒 (CCPM) 的降解速度较慢. 这种差异是由于小剂形成的无效链内交叉链,影响药物输送载体的稳定性.

科学领域:

纳米技术纳米技术
聚合物化学聚合物化学
药物输送系统药物输送系统

背景情况:

核心交联聚合物微粒 (CCPMs) 是药物输送的有希望的纳米载体.
有两种主要的交叉连接方法:使用低分子量交叉连接剂或使用互补的聚合物.
之前的研究指出了CCPM的快速降解,质疑小交联剂的效率.

研究的目的:

研究和比较由两个不同的交联方法形成的CCPM的降解机制.
阐明交叉连接策略对CCPM稳定性和降解动力学的影响.
为了确定链内交联是否会影响降解速度.

主要方法:

合成CCPM使用mPEG-b-PHPMAmLac聚合物修饰与thioesters.
通过原生化学结合 (NCL) 通过双功能囊蛋白交叉连接器进行交叉连接.
使用补充聚合物进行交叉连接.
在pH7.4和37°C下进行的降解研究,通过光散射强度监测.
降解特征的比较分析.

主要成果:

与配合聚合物形成的CCPM与与小剂交联的CCPM (半衰期约80小时) 相比,其降解动力学显著减缓 (半衰期约170小时).
观察到的小交叉连接器的快速降解表明部分无效的链内交叉链的形成.
降解归因于在生理条件下的交叉链中以基组的水解.

结论:

交叉连接方法极大地影响了CCPM的降解动力学.
小分子量交叉连接剂可能会导致由于链内交叉连接而导致不太稳定的CCPM.
选择合适的交叉连接策略对于设计稳定和有效的可降解CCPM药物递送系统至关重要.

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