破伤风类毒素阳离子葡聚糖微球的制备及载药机制研究-药学学报.PDF

药学学报 Acta Pharmaceutica Sinica 2010, 45 (9) : 1183 1187 ·1183 · 破伤风类毒素阳离子葡聚糖微球的制备及载药机制研究 * 郑春丽, 刘晓庆, 朱家壁, 赵玉娜 ( 中国 科大学 剂研究所, 江苏 南京 210009) 摘要: 制备破伤风类毒素阳离子葡聚糖微球, 并对微球的载 机制进行考察。采用乳化交联法在双水相中制 备了荷正电的甲基丙烯酸羟乙酯-葡聚糖微球, 并基于静电作用原理后载破伤风类毒素疫苗。微球的zeta 电位随 甲基丙烯酸二甲氨基乙酯加入量的增加而增大, 激光共聚焦显微实验表明, 异硫氰酸荧光素牛血清可以渗透进 入阳离子葡聚糖微球的内部, 而不能进入中性葡聚糖微球。采用后载法制备的破伤风类毒素阳离子葡聚糖微球 的包封率显著高于前载法。改变甲基丙烯酸羟乙酯-葡聚糖的取代度可以调控阳离子葡聚糖微球的体外释放行 为。 关键词: 破伤风类毒素; 阳离子微球; 静电作用; 葡聚糖微球; 包封率 中图分类号: R943 文献标识码:A 文章编号: 05 13-4870 (2010) 09-1183-05 Preparation of cationic dextran microspheres loaded with tetanus toxoid and study on the mechanism of protein loading * ZHENG Chun-li, LIU Xiao-qing, ZHU Jia-bi , ZHAO Yu-na (Pharmaceutical Research Institute, China Pharmaceutical University, Nanj ing 210009, China) Abstract: The aim of this study is to prepare cationic biodegradable dextran microspheres loaded with tetanus toxoid (TT) and to investigate the mechanism of protein loading. Positively charged microspheres were prepared by polymerization of hydroxylethyl methacrylate derivatized dextran (dex-HEMA) and dimethyl aminoethyl methacrylate (DMAEMA) in an aqueous two-phase system. The loading of the microspheres with TT was based on electrostatic attraction. The net positive surface charge increased with increasing amounts of DMAEMA. Confocal images showed fluorescein isothiocyanate labeled bovine serum albumin (FITC-BSA) could penetrate into cationic dextran microsphe