葫芦素B-聚乳酸-羟基乙酸共聚物载药纳米粒的构建与药效学评价

目的 以聚乳酸-羟基乙酸共聚物（PLGA）作为纳米制剂载体材料将葫芦素B制备成纳米粒，并考察其对HepG2肝癌细胞的抑制效果。方法 使用乳化溶剂蒸发法制备葫芦素B-PLGA载药纳米粒，以PLGA浓度（X₁）、PVA浓度（X₂）和药物浓度（X₃）作为考察因素，以载药纳米粒的粒径大小（Y₁）和包封率（Y₂）作为评价指标，应用中心复合设计-效应面法优化葫芦素B-PLGA载药纳米粒处方；测定了纳米粒的粒径分布和Zeta电位值，通过透射电镜观察其微观形态，并考察了葫芦素B-PLGA载药纳米粒的体外药物释放特性；比较了葫芦素B与葫芦素B-PLGA载药纳米粒对HepG2肝癌细胞的抑制效果。结果 葫芦素B-PLGA载药纳米粒的最优处方组成为：PLGA浓度为9.0%，PVA浓度为2.0%，药物浓度为4.5%，制备的纳米粒粒径为（145.4±15.8） nm，Zeta电位值为（-7.6±0.8） mV；透射电镜下可观察到纳米粒表面光滑，分布均匀；葫芦素B-PLGA载药纳米粒释药前期出现突释，后期平缓，48 h药物释放达到86%；葫芦素B-PLGA载药纳米粒对HepG2肝癌细胞的抑制作用显著高于葫芦素B。结论 葫芦素B-PLGA载药纳米粒可延缓药物释放，提高对HepG2肝癌细胞的抑制活性，为进一步临床研究奠定实验基础。

Construction and pharmacodynamic evaluation of cucurbitacin B-loaded PLGA nanoparticles

Objective To prepare cucurbitacin B-loaded PLGA nanoparticles by using PLGA as carrier material, and to investigate its inhibitory effect on HepG2 liver cancer cells.Methods The cucurbitacin B-loaded PLGA nanoparticles were prepared by emulsion solvent evaporation method. Taking PLGA concentration (X₁), PVA concentration (X₂) and drug concentration (X₃) as the investigation factors, the particle size (Y₁) and encapsulation efficiency (Y₂) of cucurbitacin B-loaded PLGA nanoparticles were used as evaluation indexes. The central composite design-response surface methodology (CCD-RSM) was applied to optimize the formulation of cucurbitacin B-loaded PLGA nanoparticles. The particle size distribution and Zeta potential value were determined. The microscopic morphology was observed by transmission electron microscopy. The in vitro drug release characteristics of cucurbitacin B-loaded PLGA nanoparticles were investigated. The inhibitory effects of cucurbitacin B and cucurbitacin B-loaded PLGA nanoparticles on HepG2 liver cancer cells were compared.Results The optimal formulation of cucurbitacin B-loaded PLGA nanoparticles was:PLGA concentration of 9.0%, PVA concentration of 2.0%, drug concentration of 4.5%. The particle size of (145.4±15.8) nm, and zeta potential of (-7.6±0.8) mV. Transmission electron microscopy showed that the nanoparticles were smooth and uniform in size. The release of cucurbitacin B-loaded PLGA nanoparticles was fast in the early stage, and the late release was slow. Finally, the drug release was 86% within 48 hours. The inhibitory effect of cucurbitacin B-loaded PLGA nanoparticles on HepG2 liver cancer cells was significantly higher than that of cucurbitacin B.Conclusion The cucurbitacin B-loaded PLGA nanoparticles could delay drug release and increase the inhibitory activity of HepG2 liver cancer cells, which lays the experimental foundation for further clinical research.