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

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 pH 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。

Preparation and characterization of insulin-loaded microspheres with FDKP

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 and insulin was investi-gated using the Differential Scanning Calorimeter(DSC).ResuIts 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 results from DSC study identified the interac-tion between FDKP and insulin.SEM images showed that insulin-loaded FDKP microspheres were sphere with rose shape and porosity,surface of drug - loaded microspheres was smooth,and insulin was filled into pores of blank FDKP microspheres.ConcIusion The insulin-loaded FDKP microspheres manufactured using the optimal formulation and prepa-ration conditions possess great appearance and high drug loading.