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

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.