花样结构白蛋白缓释载体的制备及在豚鼠内耳跨膜给药的应用  

Construction of flower-shaped albumin microparticles vector and its application for local drug delivery to the inner ear of guinea pig

作　　者：于湛[1] 于敏[2] 周志敏[3] 张之宝 杜博[3] 张哲[3] 熊青青[3] 

机构地区：[1]中国人民解放军第二炮兵总医院耳鼻喉科,北京100088 [2]中国医科大学卫生部细胞生物学重点实验室,医学细胞生物学教育部重点实验室,细胞生物学教研室,沈阳110001 [3]中国医学科学院生物医学工程研究所,天津300192

出　　处：《解剖科学进展》2013年第6期520-524,共5页Progress of Anatomical Sciences

基　　金：国家重大科学研究计划项目(No.2006CB933300);协和青年基金项目(No.3332013109;2012D08)

摘　　要：目的制备花样结构白蛋白（flower—shaped bovine serum albumin，FBSA）微纳材料作为载体进行内耳跨圆窗膜给药研究，为临床寻找新的药物缓释载体奠定基础。方法应用改良的去溶剂法制备FBSA微纳材料，并用荧光显微镜、电子显微镜、粒径分析仪等对其进行系统的表征。通过体外药物释放实验、MTF法来评估其细胞相容性和细胞毒性。通过小动物活体成像观察FBSA在豚鼠听泡内的扩散及在圆窗膜上的附着。结果蛋白基微纳米材料为放射状花样结构，大小约为50～80μm。空白FBSA微纳材料的zeta电位是-16．2mV，其最高的载药量和包封率分别是21．4％和40．0％，具有缓释效果。通过L929细胞的毒性实验测试提示经热变性处理固定后的材料具有更低的毒性和更好的细胞相容性。小动物活体实验可见药物在内耳中扩散及在圆窗膜表面附着。结论成功构建FBSA微纳材料载体，在治疗内耳病的局部给药方面有着良好的应用前景。Objective The flower-shaped bovine serum albumin （FBSA） microparticles were used as carrier for local drug delivery to the inner ear of guinea pig. Methods Flower-haped microparticles were prepared by improved desolvation method and confirmed by TEM, SEM and zeta-potential analyzer. Rhodamine B（RhB） was used as a model drug, heat denatmed FBSA micmparticles containing RhB were proved to be release-control with good cell compatibility. FBSA with RhB was used for hving image to investigate the penetration in vivo and attachment of panicles on the round window membrane （RWM）. Results The BSA microparticles were proved to be a flower-shaped structure with a diameter of 50-80μm, the zeta-potential of blank microparticles was - 16.2 mV. The drug loading and encapsulation efficiency was 21.4% and 40.0%, respectively. Lower cytotoxicity and improved biocompatibility was found in L929 cells. Conclusion Constructed FBSA microparticles vector was used successfully in the penetration through RWM into inner ear of guinea pigs.

关 键 词：牛血清白蛋白 微纳材料 缓释载体 圆窗膜 内耳 豚鼠 

分 类 号：R764.3[医药卫生—耳鼻咽喉科] R318.08[医药卫生—临床医学]