图8 不同载药浓度的ACPSi微胶囊在pH 2.5和pH 6.8条件下的释药曲线(IMC代表吲哚美辛)Fig.8 Drug release curves of ACPSi capsules with different drug loading concentrations at pH 2.5 and pH 6.8(IMC is indomethacin)

3 结 论

利用毛细管共挤出装置结合复凝聚法、静电吸附作用和仿生硅化的方法，成功制备得到具有肠靶向作用和缓控释特性的ACPSi复合微胶囊。该复合微胶囊粒径均一，且具有良好的单分散性。通过比较硅化前后的AC 微胶囊和ACPSi 复合微胶囊在不同pH 条件下的粒径变化，充分证明外层二氧化硅层能够有效抑制海藻酸钙基微胶囊在pH 6.8 条件下的溶胀行为。探索了ACPSi复合微胶囊的保存方法，将其保存在0.2 mol/L 的醋酸溶液中28 d 可以有效防止囊芯药物外泄。以吲哚美辛为药物模型，探究了具有不同载药浓度的ACPSi复合微胶囊在不同pH 条件下的释药行为，当pH 为2.5 时，药物释放极少，而转移至pH 6.8 的环境时，药物可持续释放，证明ACPSi复合微胶囊可以实现对药物的肠靶向缓慢释放。通过在囊壁嵌入HPMCP 肠溶微球，提供“微阀门”作用，可控制药物在不同pH 条件下的释放速率。总之，该复合微胶囊结构可控、粒径均一，具有良好的肠靶向控释特性，可以减少药物对胃的刺激，增强药物稳定性，提高药物生物利用度；并且其制备过程简单环保、成本较低，作为口服肠靶向缓控释给药系统具有良好的临床应用前景。此外本文中肠溶微球和微胶囊的制备过程具有良好的稳定性和可控性，通过采用微通道并联的方式，可以实现液滴模板的高产量生产，具有规模化制备的前景。

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