Design of microencapsulated chitosan microspheres for colonic drug delivery
Design of microencapsulated chitosan microspheres for colonic drug delivery
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DOI：
10.1016/s0168-3659(97)00203-4
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发表时间：
1998-03-02
影响因子：
10.8
通讯作者：
Alonso, MJ
中科院分区：
文献类型：
--
作者：
Lorenzo-Lamosa, ML;Remunan-Lopez, C;Alonso, MJ
在实现结肠选择性药物递送的不同方法中，使用聚合物，特别是由结肠细菌生物降解的聚合物，具有很大的前景。本文提出了一种结合特定生物降解性和ph依赖性释放的新系统。该系统由壳聚糖（CS）微核包裹在丙烯酸微球内组成。以双氯芬酸钠（SD）为模型药物，采用喷雾干燥法将其高效包裹于CS微核内，然后采用油中油溶剂蒸发法将其微胶囊化至Eudragit(R) L-100和Eudragit S-100中。CS微岩心尺寸较小（1.8 ~ 2.9 μ m），可有效包裹在Eudragit微球（152 ~ 223 μ m）内，形成多储层体系。尽管CS在酸性介质中溶解非常快，但在pH 7.4时，CS微芯的SD释放延迟，释放速度可通过改变CS分子量（MW）或CS盐的类型来调节（30-120 min内溶解50%）。此外，通过在CS微芯上涂覆乌达吉特，获得了完美的ph依赖性释放曲线。在酸性pH值下未观察到释放，但当达到Eudragit的pH溶解度时，可实现可变时间（8-12 h）的连续释放。提出了一种综合的释药机理，考虑了胶芯的溶蚀、胶芯的溶胀和SD的溶蚀及其在胶芯中的进一步扩散。红外光谱分析表明，CS的胺基与Eudragit的羧基之间存在离子相互作用，这为该体系提供了一种新的控制释放的元素。总之，这项工作为CS的修饰提供了新的途径，并为结肠给药提供了一个具有巨大潜力的新系统。(C) 1998爱思唯尔科学有限公司
Among the different approaches to achieve colon-selective drug delivery, the use of polymers, specifically biodegraded by colonic bacteria, holds great promise. In this work a new system which combines specific biodegradability and pH-dependent release is presented. The system consists of chitosan (CS) microcores entrapped within acrylic microspheres. Sodium diclofenac (SD), used as a model drug, was efficiently entrapped within CS microcores using spray-drying and then microencapsulated into Eudragit(R) L-100 and Eudragit S-100 using an oil-in-oil solvent evaporation method. The size of the CS microcores was small (1.8-2.9 mu m) and they were efficiently encapsulated within Eudragit microspheres (size between 152 and 223 mu m) forming a multireservoir system. Even though CS dissolves very fast in acidic media, at pH 7.4, SD release from CS microcores was delayed, the release rate being adjustable (50% dissolved within 30-120 min) by changing the CS molecular weight (MW) or the type of CS salt. Furthermore, by coating the CS microcores with Eudragit, perfect pH-dependent release profiles were attained. No release was observed at acidic pHs, however, when reaching the Eudragit pH solubility, a continuous release for a variable time (8-12 h) was achieved. A combined mechanism of release is proposed, which considers the dissolution of the Eudragit coating, the swelling of the CS microcores and the dissolution of SD and its further diffusion through the CS gel cores. In addition, infrared (IR) spectra revealed that there was an ionic interaction between the amine groups of CS and the carboxyl groups of Eudragit, which provided the system with a new element for controlling the release. In conclusion, this work presents new approaches for the modification of CS as well as a new system with a great potential for colonic drug delivery. (C) 1998 Elsevier Science B.V.