携紫杉醇和Herceptin高分子超声造影剂体外寻靶及体内肿瘤药物含量分析

Targeting analysis of paclitaxel loaded PLGA-COOH-targeted ultrasound contrast agent in vitro and content of paclitaxel in tumor tissue of nude mice

目的探讨携紫杉醇和Herceptin高分子造影剂(Pac-PLGA-HER)的体外寻靶能力及体内肿瘤药物含量。方法通过双乳化法及碳二亚胺法制备Pac-PLGA-HER,观察其与乳腺癌细胞MCF-7的结合能力。将25只种植有乳腺癌细胞MCF-7的裸鼠分为单纯紫杉醇(PTX)组、单纯载药微球(Pac-PLGA)组、单纯载药微球+超声(Pac-PLGA+US)组、靶向载药微球(Pac-PLGA-HER)组及靶向载药微球+超声(Pac-PLGA-HER+US)组,根据微球载药量调整到相应药物浓度,经尾静脉注入裸鼠体内,观察各组在荷瘤裸鼠肿瘤内药物含量情况。结果Pac-PLGA-HER平均粒径为(777.40±65.90)nm,包封率为(65.84±2.25)%,载药量为(6.58±0.23)%,体外寻靶实验可观察到Pac-PLGA-HER与乳腺癌细胞MCF-7大量结合。体内药物释放实验显示Pac-PLGA-HER+US组在裸鼠肿瘤内药物浓度高于其他各组(P<0.01)。结论 Pac-PLGA-HER与乳腺癌细胞MCF-7有较好的结合能力,体内药物释放实验中Pac-PLGA-HER+US组在裸鼠肿瘤内有较高的药物浓度。

Objective To prepare a kind of paclitaxel （PTX） loaded PLGA-COOH-targeted ultrasound contrast agent, and to investigate its affinity for breast cancer in vitro and content in the tumor tissue of nude mice. Methods The paclitax- el loaded PLGA-COOH-targeted ultrasound contrast agent were produced by the double emulsion technique and carbodiim- ide technique. The paclitaxel loaded PLGA-COOH-targeted ultrasound contrast agent targeting specifity to breast cancer cells was observed with confocal microscope. Twenty-five xenograft tumor-bearing nude mice were randomly divided into PTX, Pac-PLGA, Pac-PLGA＋US, Pac-PLGA-HER and Pac-PLGA-HER＋ US groups. The distribution of paclitaxel in the tumor tissue of nude mice in each group were observed. Results The average diameter of Pac-PLGA-HER was （777.40±65.90）nm. The drug entrapment efficiency was （65. 84±2.25）% and the drug-loading amount was （6.58±0.23） %. In the targeting study in vitro, the conjugation of Pac-PLGA-HER with MCF-7 cells was amount. Stastistical analysis showed that the paclitaxel content in Pac-PLGA-HER ＋ US group increased significantly compared with other groups （P〈0.01）. Conclusion The Pac-PLGA-HER can bind to breast cancer effectively in vitro, and paclitaxel concentrate in the tumor tissue in Pac-PLGA-HER＋US group is more.