盐酸博安霉素注射用原位凝胶的体内分布研究  

In vivo distribution of FITC-labeled boanmycin hydrochloride in situ gel

作　　者：王志会[1] 丁维明[2] 钱林学[1] 李眉[2] 许鸿章[2] 陈汝贤[2] 

机构地区：[1]首都医科大学附属北京友谊医院超声科,北京100050 [2]中国医学科学院、北京协和医学院医药生物技术研究所,北京100050

出　　处：《药学学报》2012年第5期634-639,共6页Acta Pharmaceutica Sinica

基　　金：国家“重大新药创制”综合性新药研究开发技术大平台资助项目(2009ZX09301-003-8-2);中央级公益性科研院所基本科研业务费专项资助项目(IMBF200802)

摘　　要：考察盐酸博安霉素(BAM)注射用原位凝胶在裸鼠体内的扩散情况以评价原位凝胶对盐酸博安霉素的阻滞作用。以荧光染料异硫氰酸荧光素(FITC)标记盐酸博安霉素,制备异硫氰酸荧光素-盐酸博安霉素偶联物(FITC-BAM),采用透析袋透析和Sephadex G25葡聚糖凝胶柱对偶联物进行分离纯化,利用基质辅助激光解析电离/飞行时间(MALDI-TOF)质谱检测偶联效果。建立裸鼠皮下肝癌移植瘤模型,应用动物体内活体光学成像系统定时检测盐酸博安霉素在裸鼠体内的特异性分布情况。MALDI-TOF质谱检测结果显示,FITC成功与BAM发生偶联,且二者偶联的分子比主要为1∶1或2∶1。活体动物成像系统观察显示,盐酸博安霉素注射用原位凝胶组FITC-BAM的扩散较普通注射液组明显延迟。研究表明,将盐酸博安霉素制备成注射用原位凝胶制剂,能够阻滞药物在体内的释放,延长作用时间。This study is to evaluate the sustained-release effect of the thermosensitive in situ gel for injection of boanmycin hydrochloride（BAM） by bioluminescence imaging in nude mice.BAM was labeled with fluorescein isothiocyanate（FITC）.The FITC-labeled BAM（FITC-BAM） was purified by dialysis and Sephadex G25 gel column,and then was identified by matrix-assisted laser desorption ionization/time of flight（MALDI-TOF）.The model of experimental hepatoma HepG-2 nude mice was established,and the optical imaging system was applied to evaluate the distribution of FITC-BAM in vivo.Results of MALDI-TOF proved that the major molecular ratio of BAM∶FITC was 1∶1 or 1∶2.Bioluminescence imaging showed that the diffusion of FITC-BAM in situ gel group was significantly delayed compared with the negative control group.This study demonstrated that the thermosensitive in situ gel can effectively delay the release of boanmycin hydrochloride,and extend the retention time in vivo.

关 键 词：盐酸博安霉素 异硫氰酸荧光素 温度敏感原位凝胶 活体成像 

分 类 号：R943[医药卫生—药剂学]