载姜黄素聚乙二醇单甲醚-聚乳酸纳米粒的制备及体内外评价

Preparation of curcumin-loaded methoxypolyethylene glycols-polylactide nanoparticle and its in vitro and in vivo evaluations

目的提高姜黄素的水溶性、体内循环时间和抑瘤效果。方法合成可生物降解的不同分子量的聚乙二醇单甲醚-聚乳酸(mPEG-PLA)作为载体和稳定剂,以制备姜黄素纳米粒。对聚合物进行表征,并对纳米粒的包封率、载药量、粒径分布、微观形态、体外释放行为、药代动力学和对肿瘤的抑制作用进行考察。结果纳米粒包封率为95%;载药量为17%;平均粒径为98 nm且分布均匀;透射电子显微镜(TEM)图像中呈规整球形;有良好的体外缓释效果,但不同分子量载体的纳米粒的释放行为差异无统计学意义(P>0.05);与裸药相比,曲线下面积(AUC)显著提高;对肿瘤的抑制率最高达到68.7%,与对照组相比,小鼠体质量差异无统计学意义(P>0.05)。结论载药纳米粒在体内外有良好的缓释效果和较高的抑瘤率,且无不良反应。

Objective To improve the water solubility, circulation time in vivo and anti-tumor effect of the curcumin. Methods Degradable methoxypolyethylene glycols-polylactide（ mPEG-PLA） with various molecular weights was synthesized as the carrier and stabilizer for preparing the curcumin nanoparticles.The polymer was characterized and the encapsulation efficiency, drug loading, distribution of size,micromorphology, in vitro release behaviors, pharmacokinetics, and anti-tumor effect of the curcumin nanoparticle were studied. Results The encapsulation efficiency was 95%; the drug loading was 17%; the mean particle size was 98 nm; and the distribution was even. Spherical particles were observed under transmission electron microscope.The in vitro release effect was satisfactory, but the differences of release behaviors of nanoparticles with carriers of different molecular weights were not statistically significant（ P 〉0. 05）.Compared to the pure curcumin, the area under the curve（AC） of the curcumin nanoparticle increased significantly and the maximum inhibiting rate towards the tumor was 68. 7%.The differences of body weights of mice of the control group and test group were not statistically significant（ P 〉0. 05）. Conclusion The release effect of curcumin nanoparticles is satisfactory both in vitro and in vivo and the inhibiting rate towards the tumor is high. No advert reactions are found.