Fabrication of Dual pH/Reduction-Responsive P(CL-co-ACL)-Based Cross-Linked Polymeric Micelles for PTX Delivery

作者：Fang Chen, Li Yin, Teng He, Tao Chen, Hangbo Yue, Chufen Yang · 发表于：Langmuir · 年份：2023 · DOI：10.1021/acs.langmuir.3c02077 · 被引用次数：8 · 研究领域：Nanoparticle-Based Drug Delivery、Advanced Polymer Synthesis and Characterization、Dendrimers and Hyperbranched Polymers

To enhance the stability of the polymeric micelles and optimize their drug-controlled release ability, three disulfide-linked polyethylene glycol methyl ether methacrylate–disulfide–poly(ε-caprolactone- co -γ-amine−ε-caprolactone) (PPEGMA-SS-P(CL- co -ACL)) polymers were synthesized and characterized by 1 H NMR, GPC, and FT-IR successfully, and their dual pH/reduction-responsive cross-linked polymeric micelles were prepared for paclitaxel (PTX) delivery by using 2,3-dimethylmaleic anhydride (DMMA) as the cross-linking agent. The PTX loading capacity (LC) and encapsulation efficiency (EE) values of the cross-linked micelles formed by PPEGMA 8 -SS-P(CL 47 - co -ACL 15 ) achieved were 23.96% and 71.58%, slightly higher than those of un-cross-linked micelles. Both particle sizes of blank micelles and in vitro drug release of PTX-loaded micelles confirmed that compared with those un-cross-linked micelles, the cross-linked micelles were more stable at pH 7.4 + 0 mM DTT, with a PTX cumulative release of 13% at 120 h, while the PTX cumulative release of the cross-linked micelles at pH 5.0 + 10 mM DTT were close to that of un-cross-linked micelles after 60 h, indicating the successful reversible cross-linking and smooth drug release of the cross-linked micelles. The cytotoxicity assay showed that PPEGMA 8 -SS-P(CL 47 - co -ACL 15 ) and its cross-linked micelles had low cell cytotoxicity, and both PTX-loaded micelles revealed a certain inhibitory effect on HepG2 cells. These results re...