Liu Xingzheng, Fan Rongrong, Lu Boting, Le Yuan
State Key Laboratory of Organic-Inorganic Composites, Beijing University of Chemical Technology, North Third Ring Road 15, Chaoyang District, Beijing 100029, China.
Pharmaceutics. 2018 Nov 13;10(4):230. doi: 10.3390/pharmaceutics10040230.
Methoxy-poly(ethylene glycol)-poly(l-glutamic acid)-poly(l-phenylalanine) triblock polymers with different architecture were synthesized as drug carrier to obtain sustained and controlled release by tuning the composition. These triblock polymers were prepared by ring opening polymerization and poly(ethylene glycol) was used as an initiator. Polymerization was confirmed by ¹H NMR, FT-IR and gel penetration chromatography. The polymers can self-assemble to form micelles in aqueous medium and their critical micelle concentrations values were examined. The micelles were spherical shape with size of 50⁻100 nm and especially can arranged in a regular manner. Sorafenib was selected as the model drug and the drug loading performance was dependent on the composition of the block copolymer. In vitro drug release indicated that the polymers can realize controlled and sustained drug release. Furthermore, in vitro cytotoxicity assay showed that the polymers were biocompatible and the drug-loaded micelles can increase toxicity towards tumor cells. Confocal fluorescence microscopy assays illustrated that the micelles can be uptaken quickly and release drug persistently to inhibit tumor cell growth.
合成了具有不同结构的甲氧基聚(乙二醇)-聚(L-谷氨酸)-聚(L-苯丙氨酸)三嵌段聚合物作为药物载体,通过调节组成来实现药物的持续和控释。这些三嵌段聚合物通过开环聚合制备,聚(乙二醇)用作引发剂。通过¹H NMR、FT-IR和凝胶渗透色谱法对聚合反应进行了确认。聚合物在水性介质中可自组装形成胶束,并测定了其临界胶束浓度值。胶束呈球形,尺寸为50⁻100 nm,且尤其能规则排列。选择索拉非尼作为模型药物,药物负载性能取决于嵌段共聚物的组成。体外药物释放表明,该聚合物能够实现药物的控释和缓释。此外,体外细胞毒性试验表明,该聚合物具有生物相容性,载药胶束可增加对肿瘤细胞的毒性。共聚焦荧光显微镜分析表明,胶束能够被快速摄取并持续释放药物以抑制肿瘤细胞生长。