【摘要】 目的:通过星点设计-效应面法优化重组人血管内皮抑制素(Endostar)壳聚糖纳米粒的制备工艺。方法:以壳聚糖浓度、三聚磷酸钠(TPP)浓度及壳聚糖溶液与TPP溶液体积比为考察因素,以载药量、包封率和粒径为指标,采用多元线性回归和多元非线性回归拟合选择合适模型,并根据最佳模型绘制效应面图,选择最佳处方,并进行预测分析,同时考察最佳处方的体外释放。结果:用多元非线性回归对实验中各因素和指标进行拟合明显优于线性拟合。最佳处方制备的Endostar载药壳聚糖纳米粒,载药量、包封率及粒径的实测值与预测值的偏差均在±7%以内,体外释放1周累积释放80%。结论:通过星点设计-效应面法可以准确快速优化处方工艺。优化后的工艺制备的纳米粒可以延缓Endostar的释放,达到了缓释效果,符合预期的试验目标。更多还原

【Abstract】 Objective: To optimize the formulation of Endostar-loaded chitosan nanoparticles by central composite design-response surface methodology(CCD).Methods: The independent variables were the concentrations of chitosan and sodium triphosphate,and the volume ratio of chitosan solution and sodium triphosphate solution.The dependent variables were the drug loading,encapsulation efficiency,and particle size.Linear or nonlinear mathematic models were used to estimate the relationship between the independent and dependent variables.Response surface was delineated according to the best-fit mathematic models to select the optimized formulation and assess the observed and predicted values.The in vitro release of the optimized nanoparticles was also studied.Results: Regression coefficients of polynomial equation were superior to multi-linear equation for analyzing the variables.Bias between the observed and predicted values of the optimized formulation was within ±7%.The in vitro cumulation release of the optimized nanoparticles achieved 80% after 7 days.Conclusion: The CCD is applicable in the optimization of the formulation of Endostar nanoparticles.The in vitro release study exhibits a property of sustained release in vitro and can match expectations.更多还原