School of Chemical Engineering and Light Industry, Guangdong University of Technology, Guangzhou, 510006, PR China.
Departamento de Física de Polímeros, Elastómeros y Aplicaciones Energéticas, Instituto de Ciencia y Tecnología de Polímeros, CSIC, c/Juan de la Cierva, 3, Madrid, 28006, Spain.
Colloids Surf B Biointerfaces. 2021 Aug;204:111797. doi: 10.1016/j.colsurfb.2021.111797. Epub 2021 Apr 28.
Delivery of anticancer drugs by amphiphilic polymeric micelles with disulfide bonds as the reduction-responsive groups has potential application in the field of drug-controlled release. In this study, three disulfide-linked polycaprolactone-b-polyethylene glycol methyl ether methacrylate (PCL-SS-PPEGMA) were synthesized and confirmed by H NMR and GPC, and then used for doxorubicin (DOX) delivery. The CMC values of the three PCL-SS-PPEGMA micelles were low (0.71-4.56 mg/L), indicative of the good stability of micelles in aqueous solution. The drug loading content (LC) and encapsulation efficiency (EE), together with the DOX accelerated release profiles were determined, with good drug loading capacity and well drug-controlled release performance. And to explore the mesoscopic behavior of reduction-responsive drug-loaded polymeric micelles, by using a dedicated disulfide bond-breaking model and script, dissipative particle dynamics (DPD) simulations were carried out on the three PCL-SS-PPEGMA polymers. Their self-assembled behavior, formation of DOX-loaded micelles, the disulfide bond-breaking process, as well as the DOX reduction-responsive release process were simulated and assessed. Comparing the DPD simulation results with the experimental data, we found that they were in good agreement, effectively demonstrating that the DPD simulation method developed can provide a practical mesoscopic approach for the reduction-responsive drug-loaded polymeric micelles that involved the cleavage of dynamic covalent bonds.
具有二硫键作为还原响应基团的两亲性聚合物胶束递送抗癌药物在药物控制释放领域具有潜在应用。在这项研究中，合成了三种二硫键连接的聚己内酯-b-聚乙二醇甲基醚甲基丙烯酸酯（PCL-SS-PPEGMA），并通过 1H NMR 和 GPC 进行了确认，然后用于阿霉素（DOX）的递送。三种 PCL-SS-PPEGMA 胶束的 CMC 值较低（0.71-4.56mg/L），表明胶束在水溶液中的稳定性良好。测定了载药量（LC）和包封效率（EE）以及 DOX 的加速释放曲线，具有良好的载药能力和良好的药物控制释放性能。为了探索还原响应载药聚合物胶束的介观行为，通过使用专门的二硫键断裂模型和脚本，对三种 PCL-SS-PPEGMA 聚合物进行了耗散粒子动力学（DPD）模拟。模拟和评估了它们的自组装行为、DOX 载药胶束的形成、二硫键的断裂过程以及 DOX 的还原响应释放过程。将 DPD 模拟结果与实验数据进行比较，发现它们吻合良好，有效地证明了所开发的 DPD 模拟方法可以为涉及动态共价键断裂的还原响应载药聚合物胶束提供实用的介观方法。
