采用改进的乳化-溶剂挥发工艺制备CsA-PLA纳米载体,以包封率为指标,用Box-Behnken法优化CsA-PLA纳米载体制备工艺.采用透射电镜、Zetasizer Nano 粒度仪评价产品的形貌、表面电位、粒径及粒径分布,在HPLC法测定CsA含量基础上,开展纳米载体体外释放特性研究.Quality by Design(QbD)预测的最佳工艺参数为PLA用量115.0 mg、CsA投药量22.2 mg、二氯甲烷3.45 mL和丙酮2.55 mL.在此条件下制备的纳米载体平均粒径为(168.7±4.3) nm,zeta电位为(−16.9±0.47) mV,载药量0.323 mg⋅mg−1,载体球形度和单分散性优良,药物包封率为(90.73±0.61)%,接近预测值91.05%.在符合漏槽条件的释放介质中,CsA-PLA纳米粒呈现了pH依赖型基质溶蚀缓释特征,7 d时在模拟胃、肠液中的累积释放率分别达到41.1%和80.4%.实验证明了QbD在预测制备CsA-PLA纳米载体的潜力.%CsA-PLA nanoparticles were prepared by modified emulsification-solvent evaporation method. The optimized formula for preparation was screened by Box-Behnken design with the entrapment efficiency as the index. The Transmission Electron Microscope and Zetasizer Nano instruments were utilized to investigate the morphology and surface potential, mean particle size and size distribution of the nanoparticles, respectively. Based on determining the content of CsA with HPLC, in vitro release behavior of CsA loaded nanoparticles were studied. Optimized parameters of CsA-PLA nanoparticles preparation predicted by Quality by Design are 115.0 mg PLA, 22.2 mg CsA, 3.45 mL ethylene chloride and 2.55 mL acetone. The nanoparticles prepared under above conditions show satisfactory monodispersity and sphericity with mean size of (168.7±4.3) nm and zeta potential of (−16.9±0.47) mV. Their mean drug loading is 0.323 mg∙g-1, and the experimental value of entrapment efficiency (90.73±0.61)% is very close to the predicted value of 91.05%. Under the leaking tank condition, a kind of sustained release characteristics based on pH-dependent matrix solution was shown and cumulative release ratios of 41.1%and 80.4%in simulated gastric and intestinal media were determined at 7th day, respectively. The potential of using Quality by Design to predict and optimize the preparation parameters of CsA loaded PLA nanoparticles was experimentally proved.
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