长春碱PCL-PEG-PCL纳米粒的制备及质量评价

Preparation and evaluation of vinblastine PCL-PEG-PCL nanoparticles

目的:制备负载长春碱的PCL-PEG6000-PCL纳米粒,并研究其理化性质及体外抗肿瘤活性。方法:采用开环聚合法制备PCL-PEG6000-PCL三嵌段元共聚物,通过共沉淀法制备了长春碱的PCL-PEG6000-PCL纳米粒,并测定其形态、粒径及多分散度、粒子产率、载药率和包封率、体外释放度,采用MTT法考察长春碱纳米粒对人白血病细胞耐药株K562/A02的细胞毒性。结果:透射电镜结果表明:得到了具有核-壳结构的球形粒子,并且纳米粒的平均粒径为(185±2.7)nm,载药率和包封率分别为28.83%和86.52%,体外释放研究表明:长春碱从纳米粒中的释放量(9h)达70%以上,24h释放基本完全。负载长春碱的纳米粒对K562/A02的抑制率比同浓度下长春碱溶液组显著增加。结论:PCL-PEG-PCL纳米粒可以作为长春碱的载体,所得粒子形状规则,包封率高,性质稳定,药物释放缓慢。长春碱经过PCL-PEG-PCL纳米粒的包裹后,对K562/A02的细胞毒性显著增强。

Aim：To prepare vinblastine-loaded PCL-PEG6000-PCL nanoparticles,and to study their physicochemical properties and in vitro antitumor activity.Methods：PCL-PEG6000-PCL triblock copolymer was prepared by ring-opening polymerization,and vinblastine-loaded PCL-PEG6000-PCL nanoparticles was prepared by coprecipitation.The morphous,particle size,polydisperse index,particle yield,the drug-loading content,the encapsulation efficiency and in vitro release rate of these vinblastine-loaded nanoparticles were determined.The cytotoxicity of vinblastine-loaded nanoparticles to K562/A02 leukimia cell line was determined by MTT assay.Results：It was found using transmission electron microscopy（TEM）that the nanoparticles exhibited a spherical shape with core-shell structure.The particle sizes of the nanoparticles obtained by dynamic light scattering were（185±2.7）nm.The drug loading content and the encapsulation efficiency were determined to be 28.83% and 86.52%,respectively.In vitro release study revealed that more than 70% of accumulative release of entrapped vinblastine was reached in 9 hr and that nearly complete release was achieved in 24 hr.The inhibition of vinblastine-loaded nanoparticles to K562/A02 cell line was significantly increased as compared with that of the same dose of sulfate vinblastine solution.Conclusions：PCL-PEG-PCL nanoparticles could be used as a carrier of vinblastine,and the prepared nanoparticles exhibited a spherical shape,high encapsulation efficiency,relevant stablity and sustained-release properties.The cytotoxicity of vinblastine to K562/A02 cell line was significantly increased when it was encapsulated in PCL-PEG-PCL nanoparticles.