开环乳糖交联壳聚糖微载体的制备及肝细胞亲和性研究

Studies on the preparation of chitosan microcarriers cross-linked by oxidized lactose and culture of primary hepatocytes

以液体石蜡作分散介质,开环乳糖作交联剂,反相悬浮法制备了性能优良的壳聚糖微载体。用其进行原代大鼠肝细胞培养,利用相差显微镜和扫描电镜对培养结果进行观察,并测定了细胞的代谢活性。肝细胞在开环乳糖交联壳聚糖微载体上保持良好的球形状态,白蛋白的分泌量达到36.4μg/24h/mL,明显高于未修饰壳聚糖和Cytodex3微载体上肝细胞的白蛋白分泌量(分别为26.0和26.7μg/24h/mL),表明开环乳糖交联壳聚糖微载体是一种优良的肝细胞培养支架。

Chitosan microcarriers was prepared using oxidized lactose as cross-linking agent that was oxidized by sodium periodate. The effect of amount of oxidized lactose on the preparation of chitosan microcarriers was studied and optimized. Rat hepatocytes cultivated on the chitosan microcarriers retained spherical shape as they have in vivo. Liver-specific functions such as albumin secretion and glucose metabolism were stably maintained for seven days and these metabolic activities of hepatocytes were higher than those of hepatocytes on chitosan microcarriers cross-linked by glutaraldehyde. The results suggest that oxidized lactose could be an interesting cross-linking agent by which to cross-link chitosan thereby reducing the risk of toxic side effects causing from use of synthetic cross-linkers.