肠靶向海藻酸钙基微胶囊的制备及控释性能研究

利用毛细管共挤出技术结合静电吸附和仿生硅化的方法，制备了海藻酸钙-壳聚糖/精蛋白/二氧化硅(ACPSi)复合微胶囊。ACPSi复合微胶囊的平均粒径约3.18 mm，单分散性好，囊壁最外层的二氧化硅层可抑制其在肠液pH环境中的溶胀，增强囊的机械稳定性。将羟丙甲基纤维素邻苯二甲酸酯(HPMCP)肠溶微球作为释药“微阀门”，嵌入囊壁可以更好地控制微胶囊的释药行为。以吲哚美辛为模型药物，当药物浓度为22.5 mg/ml时，ACPSi载药微胶囊在pH 2.5模拟胃液中3 h时累计释药率仅为0.33%，而转移至pH 6.8模拟肠液中19 h时累计释药率为77.78%；囊壁嵌入HPMCP微球后，22 h时累计释药率可提高约4%。因此，该复合微胶囊具有良好的肠靶向作用和控释特性，作为口服肠靶向缓控释制剂具有良好的应用前景。

Fabrication and controlled-release properties of intestinal-targeted Ca-alginate-based capsules

Ca-alginate-chitosan/protamine/silica (ACPSi) composite microcapsules were prepared by using capillary coextrusion technology combined with electrostatic adsorption and bionic silicification. The prepared composite ACPSi capsules have good monodispersity and the average particle size is about 3.18 mm. The rigid outer silica layer of the microcapsules can effectively inhibit the capsule swelling at pH 6.8 to improve the mechanical stability of the microcapsules. In addition, drug release behavior of microcapsules can be further controlled by embedding HPMCP enteric microspheres into the shell of ACPSi capsules as “micro-valves”. When the concentration of indomethacin is 22.5 mg/ml, the cumulative release rate of the ACPSi capsules is 0.33% at pH 2.5 for 3 h, after transferring to pH 6.8 buffer solution for 19 h, the cumulative release rate reaches 77.78%. The cumulative release rate can be increased by about 4% when HPMCP microspheres embedded into the capsule shell. The proposed ACPSi composite capsules exhibit good intestinal-targeted controlled-release performance, which provides a new strategy for developing oral intestinal-targeted drug delivery systems.