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目的制备载多柔比星(Dox)聚乙二醇-聚乳酸聚乙醇酸(PEG-PLGA)纳米胶束,并研究其抗三阴性乳腺癌作用。方法以D,L-丙交酯和乙交酯为原料,采用本体聚合法合成PEG-PLGA共聚物,通过透析法制备Dox-PEG-PLGA纳米胶束;核磁共振1HNMR对其结构进行表征;透射电子显微镜观察纳米粒形态;激光粒度仪测定平均粒径、粒径分布;紫外分光度法测定纳米粒的载药率、包封率及体外释放;MTT法评价Dox-PEG-PLGA对鼠TNBC细胞4T1的细胞毒性,并通过流式细胞术和激光共聚焦显微镜检测药物内吞。结果制备的纳米胶束呈圆形,大小较为均一,平均粒径约为135 nm,载药率为(9.70±0.33)%,包封率为(71.63±1.33)%;且工艺重现性良好,在96 h下呈现缓慢释放。Dox和Dox-PEGPLGA 24 h半数抑制浓度(IC50)分别为2.355 428和14.446 3μg·mL~(-1)。结论 Dox-PEG-PLGA纳米胶束具有较小的粒径、良好的缓释性能并能显著提高抗肿瘤效能。
Objective To prepare PEG-PLGA nanomicelles loaded with Dox and study its anti-triple negative breast cancer effect. Methods D, L-lactide and glycolide were used as raw materials to synthesize PEG-PLGA copolymer by bulk polymerization. Dox-PEG-PLGA nanomicelles were prepared by dialysis method. The structure was characterized by 1H nuclear magnetic resonance (1HNMR) Electron microscopy was used to observe the morphology of nanoparticles. The average particle size and particle size distribution were measured by laser particle size analyzer. The drug loading rate, entrapment efficiency and in vitro release of nanoparticles were measured by ultraviolet spectrophotometry. The effect of Dox-PEG-PLGA on TNBC cells 4T1 cytotoxicity, and drug endocytosis was detected by flow cytometry and laser scanning confocal microscopy. Results The nanomicelles prepared were round and of uniform size. The mean diameter was about 135 nm, the drug loading rate was (9.70 ± 0.33)%, and the entrapment efficiency was (71.63 ± 1.33)%. The reproducibility was good , Showed a slow release at 96 h. The half maximal inhibitory concentration (IC50) of Dox and Dox-PEGPLGA 24 h were 2.355 428 and 14.446 3 μg · mL -1, respectively. Conclusion Dox-PEG-PLGA nanomicelles have a smaller particle size, good sustained-release properties and can significantly improve antitumor efficacy.