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[摘要]
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。
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[Abstract]
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.
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