中文摘要：

目的：探讨负载青蒿琥酯的聚乙二醇单甲醚-聚乳酸-乙醇酸亲性嵌段共聚物（mPEG-PLGA）纳米粒的制备工艺及其对人白血病K562细胞的生长抑制作用。方法：采用改良的自乳化法制备青蒿琥酯mPEG-PLGA纳米粒（Art-Nps）,应用扫描电镜表征纳米粒的形态;激光散射粒度测定仪测其粒径分布及Zeta电位;高效液相色谱法测定Art-Nps的载药量、包封率和体外释放样品;MTT法及Hoechst染色观察其对人白血病K562细胞的增殖及促凋亡作用。结果：Art-Nps为类球形实体粒子,表面光滑,平均粒径为（156.70±1.01）nm,Zeta电位为-（26.23±1.86）mV,平均载药量为（14.51±0.20）%,平均包封率为（86.51±0.50）%,体外释放规律符合Higuchi方程：Q=4.11t1/2＋27.05,R2=0.98。MTT法显示Art-Nps抑制K562细胞增殖呈时间-剂量依赖性,且作用72h后抑制率超过青蒿琥酯处理组,具有缓释作用;经不同浓度Art-Nps培养k562细胞48h后可见细胞数量明显减少,细胞大小不一,形态不规则,高倍镜可见细胞核固缩、凝集,并有凋亡小体,且随着浓度增加凋亡小体增多。结论：本研究所制Art-Nps具有粒径小、高载药量及包封率的特点,体外实验证明其可诱导人白血病K562细胞凋亡,且具有缓释作用,延长了药物对白血病细胞的作用时间,本研究为开发青蒿琥酯新剂型提供了实验依据。

英文摘要：

Objective： To investigate the characterization of Artesunate-loaded methoxy poly（ethylene glyeol）-poly（lactic-co-glycolic acid） copolymer（mPEG-PLGA） nanoparticles and the anti-tumoral activity of the Art-Nps on human leukemia k562.Methods： The Artesunate（Art） poly（ethylene glyeol-lactic-co-glycolic acid） nanoparticles were prepared by modified-Spontaneous emulsion solvent diffusion method.The shape of the nanoparticles was observed by SEM.The mean diameter and the size distribution of nanoparticles were determined by laser light scattering.The drug loading efficiency,encapsulation rate and releasing behavior of Art-Nps in vitro were examined by HPLC.The effects of Art-Nps on the proliferation of K562 cells were studied by MTT assay and Hoechst staining.Results： Artesunate loaded mPEG-PLGA nanoparticles were spheric with the mean size of（156.70±1.01）nm,zeta potential was-（26.23±1.86）mV,and the average drug loading and encapsulation efficiency were（14.51±0.20）% and（86.51±0.50）%,respectively.In vitro release behavior could be described by the Higuchi equation： Q=4.11t1/2＋27.05,R2=0.98 MTT assay showed different concentrations,different times of Art-Nps could inhibit the proliferation of K562 cells,and both have a synergistic effect,it showed that concentration was dependented with time,and the inhibition rate after 72h was exceeded to the the control group,it was showed the Art-Nps had sustained-release effect.Art-Nps of the cells（treated by12.5,25,50μg/mL） resulted in significantly higher apoptosis than blank groups.Conclusion： The Art-Nps obtained were characted with a small size and high drug loading and entrapment efficiency,in vitro release showed a good sustained-release nature,and it can inhibit the proliferation of human leukemia K562 cells in vitro,extending the time on leukemia cells.This study was provide an experimental basis for develop a new intravenous artesunate formulations.