基于壳聚糖衍生物的蛋白质药物载体材料的制备及性能

在离子液体均相体系中合成了一种新型两亲性窄分子量分布的低聚壳聚糖衍生物月桂基-琥珀酰化壳聚糖(LSCOS). 以LSCOS为载体材料, 以牛血清蛋白(BSA)为模板蛋白, 以戊二醛为交联剂, 用油包水(W/O)乳化交联法制备了包载BSA的BSA/LSCOS缓释载药微球. 通过扫描电子显微镜(SEM)、 透射电子显微镜(TEM)及紫外-可见光谱(UV-Vis)研究了BSA/LSCOS比率和戊二醛/LSCOS比率对微球的形貌结构、 包埋率、 载药率和体外药物释放特性的影响. 结果表明, 在离子液体中合成的LSCOS包覆了BSA, 形成的微球粒径约为1 μm, 微球表面随BSA用量的增加变得光滑, 随戊二醛用量的增加变得粗糙. BSA的累积释放率与BSA包载量成正比, 与交联剂添加量成反比, 因此, 可通过控制蛋白质药物的添加比率和交联剂用量来控制蛋白质药物体外释放率.

Preparation and Characterization of Chitosan Derivative Microspheres for Protein Delivery†

A novel amphiphilic narrow molecular weight distribution and low degree of polymerization lauryl-succinyl chitosan derivative(LSCOS) was synthesized in ionic liquid homogeneous system. The LSCOS microspheres were prepared according to water-in-oil emulsification cross-linking method with LSCOS as protein-loading material and bovine serum albumin(BSA) as a model protein and glutaraldehyde as the crosslinker. The effects of the BSA/LSCOS mass ratio and glutaraldehyde/LSCOS mass ratio on the morphology structure, loading capacity(LC), loading efficiency(LE) and in vitro BSA release characteristics were investigated by means of scanning electron microscopy(SEM), transmission electron microscopy(TEM) and UV-Vis spectroscopy. The results showed that LSCOS was successfully synthesized in ionic liquid and BSA-loaded LSCOS microspheres were spherical in shape with particle size approximately 1 μm. The microspheres had a smoother surface with the increasing ratio of BSA/LSCOS and a rougher surface with the increasing ratio of glutaraldehyde/LSCOS. Decrease and increase in the ratio of BSA/LSCOS and glutaraldehyde/LSCOS, respectively, resulted in the decrease of the cumulative release of BSA. The data indicated that protein release rate can be controlled by adjusting the protein ratio and the glutaraldehyde ratio. Therefore, the LSCOS synthesized in ionic liquid could be a promising material with slow-release function for protein delivery.