2,5-二酮-3,6-二(N-富马酰基-4-氨基丁基)哌嗪(FDKP)载胰岛素微球的制备及表征

Preparation and characterization of insulin-loaded microspheres with FDKP

目的制备并表征载胰岛素的2,5-二酮-3,6-二(N-富马酰基-4-氨基丁基)哌嗪(FDKP)微球。方法以FDKP作为载体,制备载胰岛素微球(FDKP-INS),利用Box-Behnken试验设计对载药微球的载药量及粒径进行筛选。使用扫描电子显微镜(SEM)对微球形态进行观察,同时以差示扫描量热法(DSC)考察胰岛素与FDKP间相互作用。结果最优处方工艺条件为:混悬液p H值为4.56,投药比为15.97%(W/W),搅拌时间为2.4 h,在此工艺条件下制备的微球载药量为13.23%,粒径为4.515μm,与预测值接近;显示扫描图谱表明,胰岛素与FDKP间存在相互作用;扫描电子显微镜显示空白FDKP微球外形呈玫瑰花球形状,形态较完整,且表面呈现多孔隙,载药微球表面较平滑,胰岛素填充入空白微球孔隙中。结论经过优化的处方工艺所制得的载胰岛素FDKP微球具有良好的外观性状和较高的载药量。

Objective To prepare and characterize insulin-loaded FDKP microspheres.Methods Insulin-loaded mi- crospheres were prepared using FDKP as the carrier material.Box-Behnken experimental design was applied to optimize the formulation and preparation conditions to yield satisfactory drug-loading and particle size.The morphology of microspheres was recorded on a Scanning Electronics Microphotograph （SEM） and the interaction between FDKP arid insulin was investigated using the Differential Scanning Calorimeter （ DSC ） .Results The optimal formulation and preparation conditions were as follows ： stirring time 2.4 h ; the ratio of FDKP and insulin （ W/W ） , 15.97% ; pH of suspension, 4.56. The drug-loading and particle size of final product were 13.23% and 4.515 μm, respectively.The resuhs from DSC study identified the interaction between FDKP and insulin.SEM images showed that insulin-loaded FDKP microspheres were sphere with rose shape and porosity, surface of drugloaded microspheres was smooth, and insulin was filled into pores of blank FDKP microspheres.Conclusion The insulin-loaded FDKP microspheres manufactured using the optimal formulation and preparation conditions possess great appearance and high drug loading.