考布他汀4A磷酸酯缓释纳米粒的制备及抗肿瘤活性考察

Preparation and Anti-tumor Activity Investigation of Combretastatin A-4P Nanoparticles Encapsulated with PLGA

目的:以聚乳酸-聚羟基乙酸共聚物(PLGA)为载体材料,制备考布他汀4A磷酸酯(CA4P)缓释纳米粒,并考察其体内外抗肿瘤活性。方法:采用W/O/W复乳-溶剂挥发法制备CA4P-PLGA纳米粒(CA4P-PLGA-NPs),通过透射电镜观察其形态,激光光散射仪测定粒径分布,HPLC测定载药量、包封率和体外累积释放率。采用MTT测定体外细胞毒活性,通过荷瘤裸鼠试验评价CA4P-PLGA-NPs体内抑瘤活性。结果:CA4P-PLGA-NPs粒径分布较窄,平均粒径113.7 nm,平均载药量(12.5±0.8)%,平均包封率(58.9±1.2)%,具有一定缓释效果。MTT和荷瘤裸鼠试验表明CA4P-PLGA-NPs具有较好的抗肿瘤活性。结论:采用W/O/W复乳-溶剂挥发法制备的CA4P-PLGA-NPs具有一定的缓释作用,抗肿瘤活性较CA4P有所提高。

Objective：To prepare combretastatin A-4P（CA4P） sustained release nanoparticles with polylactic acid-polyglycolic acid（PLGA） as carrier material,and investigate its in vitro and in vivo anti-tumor activity.Method：CA4P-PLGA-NPs were made by W/O/W double emulsion solvent evaporation method,morphology of CA4P-PLGA-NPs was observed by transmission electron microscopy,particle size distribution was measured by dynamic laser scattering instrument,drug loading,encapsulation efficiency and in vitro cumulative release rate were determined by HPLC.In vitro cytotoxic activity of CA4P-PLGA-NPs on Hela cell was measured by MTT assay,in vivo antitumor activity was evaluated by tumor-bearing nude mice test.Result：Particle size distribution of CA4P-PLGA-NPs was narrow with average particle size was 113.7 nm,average drug loading was（12.5±0.8）%,average encapsulation efficiency was（58.9±1.2）%,these data showed that CA4P-PLGA-NPs had a certain sustained-release effect.CA4P-PLGA-NPs had good in vitro and in vivo anti-tumor activity through MTT and tumor-bearing nude mice test.Conclusion：CA4P-PLGA-NPs prepared by W/O/W solvent evaporation method had sustained-release effect,its anti-tumor activity was better than CA4P.