叶酸介导肿瘤细胞靶向紫杉醇聚合物胶束的制备与表征

Preparation and Characterization of Paclitaxel-loaded Folate-conjugated Polymer Micelles as Tumor-targeted Drug Delivery System

以叶酸-聚乙二醇-二硬脂酰磷脂酰乙醇胺(FA-PEG 3350-DSPE)和甲氧基聚乙二醇-二硬脂酰磷脂酰乙醇胺(mPEG 2000-DSPE)(摩尔比1∶100)作为混合载体材料,采用固体分散-水化法,制备包载紫杉醇(1)的聚合物胶束,以星点设计-效应面法进行处方优化,并考察了聚合物胶束的理化性质、体外抑制肿瘤细胞生长效果及对巨噬细胞摄取的影响。结果表明,优化所得胶束的包封率为81%、载药量为2.7%、平均粒径为12～16 nm,可持续释放24 h;制品可有效提高1体外抑制肿瘤细胞生长的效果,加入1%的FA-PEG 3350-DSPE可略减弱mPEG 2000-DSPE规避巨噬细胞吞噬的效果。

Paclitaxel-loaded folate-conjugated polymer micelles were prepared by solid-dispersing and hydration method with folate-poly（ethylene glycol）-distearoylphosphatidylethanolamine（FA-PEG 3350-DSPE） and methoxy-poly（ethylene glycol）-distearoylphosphatidylethanolamine（mPEG 2000-DSPE）（1∶100,molar ratio） as the materials.The formulation was optimized by using the central composite design-response surface method.Micelles were characterized with respect to physico-chemical properties,inhibition of tumor cell growth in vitro and macrophage uptake.The results showed that the entrapment efficiency and drug loading of the optimized micelles were 81% and 2.7% with the average diameter of 12-16 nm.The drug was released in a sustained-release manner for 24 h.The inhibition of the micelles to tumor cell growth in vitro was significantly improved while the macrophage avoidance of mPEG 2000-DSPE was decreased by adding 1% FA-PEG 3350-DSPE.