紫杉醇纳米粒子的制备及其应用

Preparation and application of paclitaxel nanoparticles

背景:紫杉醇临床用剂型紫素易引起过敏反应,因此研制新的紫杉醇新剂型就显得十分有意义。目的:研制紫杉醇新剂型,观察其在动物模型上治疗肿瘤的效果。方法:合成具有自主知识产权的生物可降解材料医用聚己内酯。采用溶剂替代法制备载紫杉醇纳米粒子,对其粒径、形态、紫杉醇含量、体外释放等进行测定。选用TA2系实验小鼠,建立乳腺癌动物模型,随机分为5组,分别局部注射生理盐水、紫素、低剂量、中剂量及高剂量紫杉醇纳米粒子进行治疗。结果与结论:实验制备的紫杉醇纳米粒子平均粒径约为153.54nm,包埋率为87.25%,紫杉醇含量19.06%。体外可恒定释放30d以上。2周药物治疗显示,各治疗组均不同程度上抑制了肿瘤的生长,其中紫杉醇纳米粒子中、高剂量组的抑瘤率明显高于紫素治疗组(P<0.01)。提示紫杉醇纳米粒子可缓释药物,中剂量组和高剂量组对小鼠乳腺癌的抑瘤率高于紫素组。

BACKGROUND： Paclitaxel is easy to cause allergic reactions in clinic; therefore, the development of a new paclitaxel formulation appears to be very meaningful. OBJECTIVE： To prepare paclitaxel nanoparticles and to observe their therapeutic efficacy on mouse models of breast cancer. METHODS： A biodegradable poly-caprolactone was used as drug delivery material. Paclitaxel nanoparticles were prepared by solvent displacing method. The paclitaxel nanoparticles were characterized for size, drug loading capacity, and in vitro release. Trial mice were randomly divided into negative control group, paclitaxel positive control group, low-dose paclitaxel nanoparticles group, mid-dose paclitaxel nanoparticles group, and high-dose paclitaxel nanoparticles group. RESULTS AND CONCLUSION： The average size of paclitaxel nanoparticles was around 153.54 nm. The encapsulation efficiency of paclitaxel nanoparticles was 87.25%. Loading amount of paclitaxel in the paclitaxel nanoparticles was 19.06%. In vitro, nanoparticles maintained sustained release of paclitaxel for over 30 days. After 2 weeks of treatment, the inhibition of tumor growth ratio was more obvious in the mid-dose and high-dose paclitaxel nanoparticles groups than in the paclitaxel positive control group （P〈0.01）. These findings indicate that the inhibition of tumor growth ratio of paclitaxel nanoparticles （mid-dose and high-dose groups） is better than that of paclitaxel.