目的 制备负载鬼臼毒素聚乳酸-羟基乙酸共聚物纳米粒（PPT-loaded PLGA NPs），并考察其对人乳腺癌MCF-7细胞的抗肿瘤活性。方法 采用乳化–溶剂蒸发法制备PPT-loaded PLGA NPs，以聚乳酸-羟基乙酸共聚物（PLGA）、聚乙烯醇（PVA）、D-α-维生素E聚乙二醇1000琥珀酸酯（TPGS）质量浓度作为自变量，以粒径分布、包封率作为因变量，采用中心复合设计–响应面法进行处方优化。使用透射电镜观察微观形态，采用透析法考察PPT-loaded PLGA NPs在不同pH值释放介质中的体外释药特性，考察其对人乳腺癌MCF-7细胞的抗肿瘤作用。结果 PPT-loaded PLGA NPs的最优处方为：PLGA质量浓度为120.0 mg/mL，PVA质量浓度为20.0 mg/mL，TPGS质量浓度为2.5 mg/mL。制备的PPT-loaded PLGA NPs呈规则球形结构，实测粒径（163.6±4.2）nm、包封率（89.4±0.6）%。PPT-loaded PLGA NPs体外释药速率具有缓释性，48 h累积释放率达90%。PPT-loaded PLGA NPs对人乳腺癌MCF-7细胞表现出良好的体内外抗肿瘤活性。结论 成功制备了PPT-loaded PLGA NPs，其具有良好的缓释效果和体内外抗肿瘤活性。

Objective To prepare podophyllotoxin loaded PLGA nanoparticles (PPT-loaded PLGA NPs) and to evaluate the anti-tumor activity against human MCF-7 breast cancer cells. Methods PPT-loaded PLGA NPs were prepared by emulsification - solvent evaporation method. PLGA concentration, PVA concentration, and TPGS concentration were used as variable factors, particle size distribution and encapsulation rate were used as evaluation indexes, and central composite design - response surface method was used to optimize the prescription. The microscopic morphology was observed with transmission electron microscope. The in vitro release characteristics of PPT-loaded PLGA NPs in different pH value release media were investigated by dialysis method. The anti-tumor activities of PPT-loaded PLGA NPs against human MCF-7 breast cancer cells were studied. Results The optimal formulation of PPT-loaded PLGA NPs was as followed: with PLGA concentration of 120.0 mg/mL, PVA concentration of 20.0 mg/mL, and TPGS concentration of 2.5 mg/mL. PPT-Loaded PLGA NPs was distributed in a spherical shape, the average particle size was (163.6 ± 4.2) nm, and the encapsulation rate was (89.4 ± 0.6)%. The in vitro release rate of PPT-loaded PLGA NPs exhibited sustained release, with a cumulative release rate of 90% after 48 h. PPT-loaded PLGA NPs showed good antitumor activity in vitro and in vivo against human MCF-7 breast cancer cells. Conclusion PPT-loaded PLGA NPs are successfully prepared with good sustained release and anti-tumor activities in vitro and in vivo.

R282.4

湖北省卫生健康科研项目（WJ2021M218）