中心复合设计优化5-氟尿嘧啶肝动脉栓塞微球的制备工艺

Optimization of the preparation of fluorouracil-loaded gelatin microspheres for chemo-embolization therapy of hepatocellular carcinoma using central composite design

目的 应用中心复合设计优化5-氟尿嘧啶肝动脉栓塞明胶微球的制备工艺,以提高微球性质的可预测性。方法 采用乳化交联法制备,以微球载药量、粒径、包封率为因变量对明胶浓度(X1)、乳化剂的用量(X2)、乳化转速(X3)3个自变量的各水平进行多元线性回归和二项式拟合,并进行预测分析。结果 载药量、包封率和粒径拟合所得多元二次方程的复相关系数r2分别为0.949 5,0.8086,0.891 5。结论 中心复合设计法优化微球制备工艺预测性良好。

OBJECTIVE: To optimize the preparation of fluorouracil-loaded gelatin microspheres (5-FuMS) for chemo-embolization therapy of hepatocellular carcinoma using central composite design. METHODS: 5-FuMS was prepared by an emulsion-chemical-crosslinking method. The effects of gelation concentration X1, amount of emulsifier X2 and stirring speed X 3 on a number of response variables were systemically investigated. The response variables were drug loading, loading efficiency and geometric mean diameter, respectively. A desirability function that combines these three response variables was constructed. A second-order polynomial equation was fitted to the data, and the resulting equation was used to predict the responses in the optimal region. RESULTS: All the investigated response variables were found to be highly dependent on the formulation variables. CONCLUSION: The central composite design was successfully used to optimize the preparation of 5-FuMS.