马钱子碱mPEG-PLGA纳米粒的构建与体外抗肿瘤细胞活性研究

Construction of brucine-loaded mPEG-PLGA nanoparticles and its antitumor activity in vitro

目的本研究作者利用甲氧基聚(乙二醇)(mPEG)-聚(乳酸-羟基乙酸共聚物)(PLGA)制备载有马钱子碱的两亲性嵌段共聚物纳米粒,并评价其对肝肿瘤HepG2细胞的体外抗肿瘤效果。方法采用溶剂蒸发-薄膜分散法制备负载马钱子碱mPEG-PLGA纳米粒,通过透射电镜观察其微观形态,马尔文激光粒度仪测定其粒径分布及ζ电位,并采用反向透析法考察了马钱子碱mPEG-PLGA纳米粒在pH7.4释放介质中的体外释药特性;评价了肝肿瘤HepG2细胞对马钱子碱mPEG-PLGA纳米粒的摄取能力,比较了马钱子碱mPEG-PLGA纳米粒与马钱子碱对肝肿瘤HepG2细胞的体外抗肿瘤效果。结果制备的负载马钱子碱mPEG-PLGA纳米粒呈圆整球状分布,包封率为(95.4±1.6)%,平均粒径为(118.4±15.7)nm,ζ电位为(-24.4±0.5)mV;马钱子碱mPEG-PLGA纳米粒在前期药物释放较快,后期较为平缓;肝肿瘤HepG2细胞对马钱子碱mPEG-PLGA纳米粒具有较强的摄取能力,且马钱子碱mPEG-PLGA纳米粒对肝肿瘤HepG2细胞的抑制作用显著高于马钱子碱。结论本研究制备的马钱子碱mPEG-PLGA纳米粒对肝肿瘤HepG2细胞抑制更显著,具有潜在的临床应用价值,值得进一步研究。

Objective In this study,methoxy poly(ethylene glycol)(mPEG)-poly(lactic-co-glycolic acid copolymer)(PLGA)was used to prepare amphiphilic block copolymer nanoparticles loaded with brucine.And the antitumor activity of liver cancer HepG2 cells in vitro was evaluated.Methods The brucine-loaded mPEG-PLGA nanoparticles were prepared by solvent evaporation-film dispersion method.The microscopic morphology was observed by transmission electron microscopy,and the particle size distribution and Zeta potential were measured by Malvern laser particle size analyzer.The in vitro release characteristics of brucine-loaded mPEG-PLGA nanoparticles in pH7.4 PBS were investigated by reverse dialysis.The cell uptake ability of liver cancer HepG2 cells to brucine-loaded mPEG-PLGA nanoparticles was evaluated.The anti-tumor effect of brucine-loaded mPEG-PLGA nanoparticles and brucine on liver cancer HepG2 cells was compared.Results The brucine-loaded mPEG-PLGA nanoparticles were spherically distributed with an encapsulation efficiency of(95.4±1.6)%,an average particle size of(118.4±15.7)nm,and a Zeta potential of(-24.4±0.5)mV.The drug release was faster in the early stage and slower in the later stage.The liver cancer HepG2 cells had strong cell uptake ability to brucine-loaded mPEG-PLGA nanoparticles.The inhibitory effect of brucine-loaded mPEG-PLGA nanoparticles on liver cancer HepG2 cells was significantly higher than that of brucine.Conclusion This study demonstrated that the prepared brucine-loaded mPEG-PLGA nanoparticles had significant antitumor activity,which had potential clinical application value and deserved further study.