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载多柔比星PEG-PLGA纳米胶束制备及其抗三阴性乳腺癌作用 被引量:3

Preparation and anti-triple negative breast cancer of doxorubicin loaded PEG-PLGA nanoparticles
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摘要 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。 AIM To prepare doxorubicin(Dox) loaded polyethylene glycol-polylactic acid(PEG-PLGA) nano micelles,and study its therapeutic effect on triple negative breast cancer(TNBC).METHODS D,L-lactide and glycolide used as raw material for synthesis of PEG-PLGA copolymer polymerization through bulk polymerization method,Dox-PEG-PLGA micelles was prepared through dialysis method.Its structure was characterized by nuclear magnetic resonance ~1HNMR,the morphology of nanoparticles was observed by transmission electron microscope(TEM),and the particle size and particle size distribution were measured by laser granulometer.Drug loading rate(LC),encapsulation efficiency(EE) releasing and in vitro were detected by UV spectrophotometer.The cytotoxicity of Dox-PEG-PLGA micelles was evaluated with murine triple negative breast cancer 4T1 cells using a MTT based assay,flow cytometry and confocal laser scanning microscopy were used to detect the cell uptake.RESULTS The nanoparticles were uniform spherical particles.Mean diameter of nanoparticles were 135 nm,EE was(9.70±0.33) %,and LC was(71.63±1.33) %.It showed slow release compared to free drugs in 96 h.Moreover,the IC50 values of Dox and Dox-PEG-PLGA were 2.355 428 μg·mL^(-1) and 14.446 3 μg·mL^(-1),respectively.CONCLUSION Dox-PEG-PLGA nanoparticles are found to have smaller particles size and sustained release of Dox,and this can improve its cytotoxicity on triple negative breast cancer.
作者 苏博 赵婧彤 时国王 刘轶 张海山 SU Bo ZHAO Jing-tong SHI Guo-wang LIU Yi ZHANG Hai-shan(China-Japan Union Hospital of Jilin University, Changchun JILIN 130033, China)
出处 《中国新药与临床杂志》 CSCD 北大核心 2017年第10期609-613,共5页 Chinese Journal of New Drugs and Clinical Remedies
关键词 多柔比星 三阴性乳腺癌 乳腺肿瘤 纳米粒子 doxorubicin triple negative breast cancer breast neoplasms nanoparticles
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