叶酸修饰多柔比星聚合物胶束的制备及体外抗肿瘤活性评价

Preparation and in vitro Anti-tumor Activity Evaluation of Folate-conjugated Polymeric Micelles Loaded with Doxorubicin

合成了叶酸-聚乙二醇-二硬脂酰磷脂酰乙醇胺(Folate-PEG-DSPE),并用其作为靶向肿瘤的功能性材料,以甲氧基聚乙二醇-二硬脂酰磷脂酰乙醇胺(MPEG-DSPE)作为骨架材料,采用成膜水化法制备载多柔比星(1)胶束。所得胶束呈球状结构,粒径为(20±5)nm,叶酸修饰和非叶酸修饰胶束的包封率和载药量分别为(78.8±1.52)%、(79.2±147)%和(1 3.6±1.26)%、(1 3.9±1.19)%。流式细胞结果显示,分别给予游离罗丹明B(Rh B)、叶酸修饰和非叶酸修饰的载RhB胶束,摄取荧光的巨噬细胞分别占细胞总数的36.6%、1.5%和4.4%,说明聚合物胶束可显著减弱巨噬细胞的吞噬作用。体外抗KB人口腔上皮癌细胞活性的试验结果显示,1、叶酸修饰和非叶酸修饰胶束的IC_(50)分别为29 7、0.61和4.12μmol/L,表明叶酸修饰的聚合物胶束能显著提高1的抗肿瘤活性。

The block copolymer,folate-polyethylene glycol-distearoyl phosphatidylethanolamine(Folate-PEG-DSPE) was synthesized.The polymeric micelles loaded with doxorubicin(1) were prepared by the thin-film hydration method with methoxy-polyethylene glycol-distearoyl phosphatidylethanolamine(MPEG-DSPE) as the carrier and Folate-PEG -DSPE as target material.The prepared micelles were uniform and spherical with a mean diameter of(20±5)nm.The encapsulation and drug loading were(78.8±1.52)%and(13.6±1.26)%for folate-conjugated micelles,(79.2±1.47)% and(13.9±1.19)%for folate-unconjugated micelles.The fluorescence rate of rhodamine B(Rh B),folate-conjugated and folate-unconjugated micelles loaded with Rh B detected by flow cytometry were 36.6%,1.5%and 4.4%,which indicated that the micelles could avoid phagocytosis by macrophages.The results of in vitro cytotoxicity test with KB cells showed that the values of IC_(50) of 1,folate-conjugated and folate-unconjugated micelles loaded with 1 were 29.7,0.61 and 4.12μmol/L,which indicated that the anti-tumor activity of 1 could be significantly enhanced with folate-conjugated polymeric micelles as carrier.