Shu X Z, Zhu K J
Department of Polymer Science and Engineering, Zhejiang University, Hangzhou 310027, People's Republic of China.
Int J Pharm. 2002 Feb 21;233(1-2):217-25. doi: 10.1016/s0378-5173(01)00943-7.
By adopting a novel chitosan cross-linked method, i.e. chitosan/gelatin droplet coagulated at low temperature and then cross-linked by anions (sulfate, citrate and tripolyphosphate (TPP)), the chitosan beads were prepared. Scanning electron microscopy (SEM) observation showed that sulfate/chitosan and citrate/chitosan beads usually had a spherical shape, smooth surface morphology and integral inside structure. Cross-sectional analysis indicated that the cross-linking process of sulfate and citrate to chitosan was much faster than that of TPP due to their smaller molecular size. But, once completely cross-linked, TPP/chitosan beads possessed much better mechanical strength and the force to break the beads was approximately ten times higher than that of sulfate/chitosan or citrate/chitosan beads. Release media pH and ionic strength seriously influenced the controlled drug release properties of the beads, which related to the strength of electrostatic interaction between anions and chitosan. Sulfate and citrate cross-linked chitosan beads swelled and even dissociated in simulated gastric fluid (SGF) and hence, model drug (riboflavin) released completely in 5 h; while in simulated intestinal fluid (SIF), beads remained in a shrinkage state and drug released slowly (release % usually <70% in 24 h). However, swelling and drug release of TPP/chitosan bead was usually insensitive to media pH. Chitosan beads, cross-linked by a combination of TPP and citrate (or sulfate) together, not only had a good shape, but also improved pH-responsive drug release properties. Salt weakened the interaction of citrate, especially sulfate with chitosan and accelerated beads swelling and hence drug release rate, but it was insensitive to that of TPP/chitosan. These results indicate that ionically cross-linked chitosan beads may be useful in stomach specific drug delivery.
通过采用一种新型的壳聚糖交联方法，即壳聚糖/明胶液滴在低温下凝固，然后通过阴离子（硫酸盐、柠檬酸盐和三聚磷酸钠（TPP））进行交联，制备了壳聚糖珠。扫描电子显微镜（SEM）观察表明，硫酸盐/壳聚糖和柠檬酸盐/壳聚糖珠通常呈球形，表面形态光滑，内部结构完整。横截面分析表明，由于硫酸盐和柠檬酸盐的分子尺寸较小，它们与壳聚糖的交联过程比TPP快得多。但是，一旦完全交联，TPP/壳聚糖珠具有更好的机械强度，打破珠子所需的力比硫酸盐/壳聚糖或柠檬酸盐/壳聚糖珠高约十倍。释放介质的pH值和离子强度严重影响珠子的控释性能，这与阴离子和壳聚糖之间的静电相互作用强度有关。硫酸盐和柠檬酸盐交联的壳聚糖珠在模拟胃液（SGF）中膨胀甚至解离，因此，模型药物（核黄素）在5小时内完全释放；而在模拟肠液（SIF）中，珠子保持收缩状态，药物释放缓慢（24小时内释放率通常<70%）。然而，TPP/壳聚糖珠的膨胀和药物释放通常对介质pH不敏感。由TPP和柠檬酸盐（或硫酸盐）组合交联的壳聚糖珠不仅形状良好，而且改善了pH响应性药物释放性能。盐减弱了柠檬酸盐，尤其是硫酸盐与壳聚糖的相互作用，加速了珠子的膨胀，从而提高了药物释放速率，但对TPP/壳聚糖珠的影响不敏感。这些结果表明，离子交联的壳聚糖珠可能在胃特异性药物递送中有用。
