紫杉醇PLGA微球制备及荷Hep-2喉癌裸鼠体内疗效评估

Preparation of paclitaxel loaded PLGA microspheres and its efficacy in Hep-2 laryngeal squamous cell carcinoma-bearing nude mice

目的以乳酸-羟基乙酸共聚物[poly(lactic-co-glycolic acid),PLGA]为载体,制备紫杉醇缓释微球,并评估紫杉醇微球瘤内直接注射对裸鼠Hep-2移植瘤的疗效。方法采用改良溶剂蒸发法制备紫杉醇PLGA缓释微球,考察微球的体外性质,并对Hep-2移植瘤分别采用紫杉醇针剂腹腔内多次注射、紫杉醇针剂瘤内一次注射和紫杉醇微球瘤内一次注射治疗。结果制得的微球形态圆整,载药量、包封率、平均粒径和跨距分别为1.53%、97.29%、42.72μm和0.95。药物体外释放30d累计释放达到53.53%。给药3周后,与生理盐水瘤内注射组相比,紫杉醇治疗各组的肿瘤体积和重量均明显减小(P<0.05),肿瘤体积3倍增时间(TT)均明显延长(P<0.01);低剂量紫杉醇微球瘤内注射组的TT明显大于紫杉醇针剂瘤内和腹腔注射组(P<0.05);高剂量紫杉醇微球瘤内注射组的TT明显大于其它紫杉醇治疗各组(P<0.01)。紫杉醇针剂腹腔给药组、紫杉醇针剂瘤内注射组、低剂量和高剂量微球瘤内注射组的抑瘤率分别为35.99%,39.37%,47.83%和59.90%。PLGA空白微球不影响肿瘤的生长。实验未发现明显的毒性反应。结论紫杉醇PLGA微球满足缓释长效的要求,肿瘤内直接注射该多聚物给药系统可提高紫杉醇抗喉鳞状细胞癌的疗效。

Purpose Poly（lactic-co-glycolic acid）（PLGA） was used to develop paclitaxel loaded sustained-release microspheres and to investigate the efficacy of the polymer delivered iritratumorally against Hep-2 xenografts in nude mice. Methods PLGA microspheres containing paclitaxel were prepared by modified solvent evaporation method. The in vitro characteristics were evaluated. Tumor nodules were treated by multiple intraperitoneal or a single intratumoral administration of paclitaxel injection or a single intratumoral injection of paclitaxel loaded PLGA microspheres. Results Spherical microspheres with smooth surface were obtained. The drug loading, encapsulation efficiency, mean diameter and span of dispersity was 1.53 % 1 97. 29%, 42.72 μm and 0.95, respectively. The cumulative release from microspheres was 53.53 % during 30-day period. Compared with the physiological saline control group, the tumor size and the tumor weight of the groups treated with paclitaxel injection or microspheres was significantly reduced（P〈0.05） and the tumor volume.tripling time（TT） was significantly prolonged（P〈0.01）. The TT of the group receiving intratumoral injection of paclitaxel microspheres at low dose was significantly increased compared to the paclitaxel injection groups by intratumoral or intraperitoneal administration（P〈0.05）. The TT of the group treated with paclitaxel microspheres at high dose was significantly increased compared to other paclitaxel treated groups（P〈 0.01）. The tumor inhibition rates of groups treated with ip paclitaxel injection, it paclitaxel injection,it paclitaxel-loaded PLGA microspheres at low and high doses were 35.99%, 39.37%, 47.83% and 59.90%, respectively. PLGA blank microspheres had no effect on the tumor growth. No significant toxic reactions were observed in the experiment. Conclusions Paclitaxel loaded sustained-release microspheres were successfully prepared. Intratumoral administration of the polymer delivery system enhances the efficacy of paclitaxel against laryngeal squamous cell carcinoma.