载HCPT纳米粒的制备及其体外抗肿瘤活性研究

The Preparation and in Vitro Antitumor Activity of HCPT Loaded Nanoparticles

目的:制备载羟基喜树碱(HCPT)的PLGA-hyd-PEG-FA纳米粒(HCPT@PLGA-hyd-PEG-FA),并对其体外抗肿瘤活性进行研究。方法:采用乳化溶剂挥发法制备HCPT@PLGA-hyd-PEG-FA,通过单因素试验考察超声功率、聚合物浓度、PVA浓度、水相和油相体积比及投药量对纳米粒粒径的影响;采用zeta电位及激光粒度分析仪测定纳米粒的粒径及zeta电位,用透射电镜(TEM)观察其形态;采用透析法评价HCPT@PLGA-hyd-PEG-FA的体外释药特性;采用MTT法测定HCPT@PLGA-hyd-PEG-FA对HepG2细胞的细胞毒性。结果:HCPT@PLGA-hyd-PEG-FA平均粒径约为109±3 nm,zeta电位为-11.57 mV,载药量为5.6%,TEM显示其为球形;体外释药结果表明HCPT@PLGA-hyd-PEG-FA对HCPT的释放具有p H值依赖性;HCPT和HCPT@PLGA-hyd-PEG-FA的IC50值分别为474.6 ng/mL和286.0 ng/mL。结论:HCPT@PLGA-hyd-PEG-FA体外释药性能良好,HCPT@PLGA-hyd-PEG-FA的细胞毒性明显大于游离的HCPT,值得进一步研究。

Objective： To prepare the 10-hydroxycamptothecin （HCPT） loaded nanoparticles based on PLGA-hyd-PEG-FA （HCPT@PLGA-hyd-PEG-FA） and to evaluate its antitumor activity in vitro. Methods： HCPT@PLGA-hyd-PEG-FA was prepared by emulsification-solvent evaporation method. Then the ultrasonic power, polymer concentration, PVA concentration, volume ratio of aqueous phase to oil phase and drug dosage were optimized. The particle size and zeta potential were detected by Laser Particle Size Analyzer, the morphology of the nanoparticle was observed by Transmission Electron Microscopy （TEM）. The in vitro drug release property of HCPT@PLGA-hyd-PEG-FA was evaluated by the dialysis method. The MTT assay was used to estimate the cytotoxicity of HCPT@PLGA-hyd-PEG-FA in HepG2 cells. Results： HCPT@PLGA-hyd-PEG-FA was spherical in shape. The mean size was 109±3 nm. The zeta potential was -11.57 mV, and the drug loading was 5.6%. The drug release of HCPT@PLGA-hyd-PEG-FA showed a pH-dependent manner. The IC50 of HCPT@PLGA-hyd-PEG-FA and HCPT were 286.0 ng/mL and 474.6 ng/mL, respectively. Conclusion： The drug release characteristic of HCPT@PLGA-hyd-PEG-FA was satisfied in vitro. The HCPT@PLGA-hyd-PEG-FA showed much greater cytotoxicity than free HCPT at the same concentration, and it is worth of further investigating.