Centre for Biomedical Engineering , Indian Institute of Technology Delhi , New Delhi 110016 , India.
Biomedical Engineering Unit , All India Institute of Medical Sciences , New Delhi 110029 , India.
Biomacromolecules. 2018 Jul 9;19(7):2549-2566. doi: 10.1021/acs.biomac.8b00178. Epub 2018 Apr 18.
In the present work, polymersomes based on self-assembled, folate-targeted, redox-responsive, ATRP-based amphiphilic diblock copolymer poly(polyethylene glycol)-S-S-polylactide with disulfide linkage were developed for efficient doxorubicin (DOX) delivery and compared with marketed DOXIL nanoformulation. The polymersomes formulation was optimized by quality by design approach providing monodisperse nanostructures of ∼110 nm and enhanced DOX loading of ∼20%. Polymersomes showed excellent stability as per the ICH guidelines over the extended storage period of 3 months. The in vitro drug release profile confirmed the redox sensitive behavior of polymersomes providing ∼80% drug release in endosomal pH 5 with 10 mmol GSH as compared to ∼20% release at pH 7.4. The targeted polymersomes achieved enhanced cellular internalization in folate receptor overexpressing cell lines, MDA-MB-231 and HeLa, providing ∼24% higher tumor reduction than DOXIL in Ehrlich ascites tumor bearing Swiss albino mice.
在本工作中，制备了基于自组装、叶酸靶向、氧化还原响应、基于 ATRP 的两亲性嵌段共聚物聚（聚乙二醇）-S-S-聚乳酸（二硫键连接）的聚合物囊泡，用于高效阿霉素（DOX）递送，并与市售的 DOXIL 纳米制剂进行了比较。通过质量源于设计方法对聚合物囊泡配方进行了优化，提供了约 110nm 的单分散纳米结构和增强的约 20%的 DOX 载药量。聚合物囊泡在延长的 3 个月储存期内按照 ICH 指南显示出极好的稳定性。体外药物释放曲线证实了聚合物囊泡的氧化还原敏感行为，与 pH7.4 相比，在 pH5 的内体中提供了约 80%的药物释放，而在 10mmol GSH 时释放约 20%。靶向聚合物囊泡在叶酸受体过表达的细胞系 MDA-MB-231 和 HeLa 中实现了增强的细胞内化，在瑞士白化病小鼠的艾氏腹水瘤中提供了比 DOXIL 约 24%的肿瘤减少。
