具有泵送控释特性的肠靶向海藻酸钙基Janus胶囊

Ca-Alginate-Based Janus Capsules with a Pumping Effect for Intestinal-Targeted Controlled Release

本研究成功开发了一种具有泵送控释特性的新型肠靶向θ型胶囊,用于疏水性药物的可控释放。该胶囊由海藻酸钙-壳聚糖/鱼精蛋白/二氧化硅(ACPSi)复合壳和呈θ形状的两个腔室组成(θ-ACPSi),两个腔室分别封装有药物和助推剂。肠溶性羟丙甲纤维素酞酸醋(HPMCP)微球嵌入到药室的外壳中。θ-ACPSi的外壳在胃部环境中为所封装的药物提供了更好的保护,而在肠道中表现出出色的肠靶向药物释放特性。以吲哚美辛为模型药物、聚丙烯酸(PAA)为助推剂,药室壳层“微通道”的打开和助推室中PAA的溶胀均有助于提高高浓度吲哚美辛的释放速率,保证了吲哚美辛在小肠部位具有恒定的释放速率。在胃中(pH=2.5),只有不到1%的吲哚美辛被释放。然而,当θ-ACPSi胶囊进入小肠(pH=6.8)时,药室外壳中的HPMCP微球因溶解而打开“微通道”,而PAA溶胀以提供泵送动力。结果,超过60%的吲哚美辛在小肠中以恒定速度释放。所制备的θ-ACPSi胶囊为开发响应型泵送控释系统和肠靶向药物递送系统提供了一种潜在的新型模式。

A novel intestinal-targeted h-shaped capsule with a pumping effect for the controlled release of hydrophobic drugs is successfully developed.The proposed capsule is composed of a Ca-alginate–chitosan/protamine/silica(ACPSi)composite shell and two chambers forming a h-shape(h-ACPSi),which respectively encapsulate drugs and booster agents.Enteric hydroxypropyl methylcellulose phthalate(HPMCP)microspheres are embedded into the drug chamber shell.The h-ACPSi composite shell offers improved protection for the encapsulated drug in the stomach environment and excellent intestinaltargeted drug release.Using indomethacin as the model drug and polyacrylic acid(PAA)as the booster agent,both the opening of‘‘microchannels”in the drug chamber and the swelling of PAA in the booster chamber increase the release rate of high-concentration indomethacin and ensure a constant release of indomethacin in the small intestine.In the stomach(pH 2.5),less than 1%of the indomethacin is released.However,when the h-ACPSi capsules enter the small intestine(pH 6.8),the HPMCP microspheres in the drug chamber shell dissolve to open the‘‘microchannels,”while the PAA swells to provide pumping impetus.As a result,more than 60%of the indomethacin is released at a constant speed in the small intestine.The proposed h-ACPSi capsules provide a potential and novel model for developing responsive pumping controlled-release systems and intestinal-targeted drug delivery systems.