Chen Chen, Liu Mingzhu, Lii Shaoyu, Gao Chunmei, Chen Jiucun
a State Key Laboratory of Applied Organic Chemistry, Key Laboratory of Nonferrous Metal Chemistry and Resources Utilization of Gansu Province , Lanzhou , 730000 , P. R. China.
J Biomater Sci Polym Ed. 2012;23(16):2007-24. doi: 10.1163/092050611X601720. Epub 2012 May 11.
Hydrogels based on sodium alginate (SA) have already been widely used in biomedical applications using Ca(2+) as a cross-linker; however, these hydrogels tend to disintegrate in electrolyte solutions. To solve this problem, we present a kind of oxidized sodium alginate (OSA) microgel using water-soluble chitosan (WSC) as a cross-linker. This microgel was successfully prepared via an emulsion cross-linking technique at room temperature. The microgel was cross-linked by the formation of both Schiff base bonds and inter-polyelectrolyte complexes, which can efficiently eliminate the disintegration of the microgel in electrolyte solutions. Morphological properties of the resulting microgels were determined by transmission electron microscopy (TEM), hydrodynamic diameters of the microgels were characterized by dynamic light scattering (DLS). The objective of this work was to achieve the colon-specific delivery of an anti-ulcerative colitis drug. 5-Aminosalicylic acid (5-ASA) was chosen as a model drug and the in vitro drug-release profile was established in buffer solutions with 0.1 M HCl/NaCl (pH 1.2) and 0.1 M phosphate-buffered saline (PBS, pH 7.4) at 37°C. The microgel was incubated in 0.1 M PBS (pH 7.4) at 37°C to determine its degradation behavior. Cell cytotoxicity (tested by MTT assay) showed that this microgel had no significant cytotoxicity. These results indicated that this microgel prepared by introducing WSC into OSA may have potential applications in oral controlled drug-delivery systems. Therefore, the OSA/WSC microgel may be a useful carrier for the colon-specific delivery of anti-inflammatory drugs including 5-ASA and the enhanced therapeutic effect of ulcerative colitis.
基于海藻酸钠（SA）的水凝胶已经在生物医学应用中广泛使用，以Ca(2+)作为交联剂；然而，这些水凝胶在电解质溶液中容易分解。为了解决这个问题，我们提出了一种使用水溶性壳聚糖（WSC）作为交联剂的氧化海藻酸钠（OSA）微凝胶。这种微凝胶通过乳液交联技术在室温下成功制备。微凝胶通过席夫碱键和聚电解质间复合物的形成进行交联，这可以有效消除微凝胶在电解质溶液中的分解。通过透射电子显微镜（TEM）测定所得微凝胶的形态学性质，通过动态光散射（DLS）表征微凝胶的流体动力学直径。这项工作的目的是实现抗溃疡性结肠炎药物的结肠特异性递送。选择5-氨基水杨酸（5-ASA）作为模型药物，并在37°C下于0.1 M HCl/NaCl（pH 1.2）和0.1 M磷酸盐缓冲盐水（PBS，pH 7.4）的缓冲溶液中建立体外药物释放曲线。将微凝胶在37°C下于0.1 M PBS（pH 7.4）中孵育以确定其降解行为。细胞毒性（通过MTT法测试）表明这种微凝胶没有明显的细胞毒性。这些结果表明，通过将WSC引入OSA制备的这种微凝胶可能在口服控释药物递送系统中具有潜在应用。因此，OSA/WSC微凝胶可能是用于结肠特异性递送包括5-ASA在内的抗炎药物以及增强溃疡性结肠炎治疗效果的有用载体。
