干扰素经鼓室给药靶向脑的初步研究  

Preliminary Study on Brain-targeted Delivery of Human Interferon α2b Following Intratympanic Administration

作　　者：陈钢[1] 牧磊[1] 陆春燕[2] 杨帆[1] 臧林泉[1] 丁静[1] 

机构地区：[1]广东药学院药科学院,广州510006 [2]安徽安科生物工程(集团)股份有限公司,合肥230088

出　　处：《中国药学杂志》2010年第24期1922-1925,共4页Chinese Pharmaceutical Journal

基　　金：国家自然科学基金资助项目(30801553);广东省自然科学基金资助项目(07301575);广东省医学科研基金资助项目(B2007090;B2008080);广东药学院师资队伍建设经费资助

摘　　要：目的探寻干扰素经鼓室给药途径输送至脑部的可行性,为大分子药物的脑靶向提供一条全新的途径。方法采用双抗体夹心酶联免疫吸附法测定豚鼠体内各组织中人干扰素α2b的含量。经鼓室和静脉注射人干扰素α2b,测定药物在脑脊液(CSF)、脑组织、内耳外淋巴液和血清中的浓度及药动学参数。结果鼓室给药相比静脉给药,干扰素在脑部的局部生物利用度显著提高,鼓室给药后CSF和脑组织的药-时曲线下面积(AUC)分别比静脉给药高7.7、4.5倍。并且,鼓室给药能延长干扰素的作用时间,鼓室给药后CSF和脑组织的平均滞留时间(MRT)分别比静脉给药增加0.5、1.2倍。而且,鼓室给药后干扰素在血清中分布大大减少,其AUC比静脉给药低84.5%。结论经鼓室给药有望成为大分子药物一种新的脑靶向方法,值得进一步研究。OBJECTIVE To investigate the feasibility of delivering interfei＇on （ IFN ）α2b to the brain following intratympanic administration, and provide a novel route for macromolecular drugs targeting the brain tissues. METHODS IFNα2b solutions were administered after intratympanic and intravenous injection in guinea pigs. Cerebrospinal fluid （CSF） , brain tissues, perilymph, and ser- um were collected periodically. The concentrations were measured by the double antibody sandwich enzyme-linked immunosorbent assay （ELISA） , and used to estimate phannacokinetic parameters of IFN. RESULTS The AUCs （area under curve） of IFN in CSF and brain tissues following intratympanic administration were increased by 7.7 and 4. 5-fold, compared with intravenous administration. After intratympanic administration, the MRT （ mean residence time） of IFN in CSF and brain tissues were respectively extended by 0. 5 and 1.2 times compared with intravenous administration. Moreover, the AUC of IFN in serum following intratympanic administration was decreased by 84.5% tollowing intravenous administration. CONCLUSION Intratympanic administration shows great potential and offers a promising alternative to brain-targeted delivery of macromolecular drugs.

关 键 词：人干扰素α2b 脑靶向 鼓室给药 双抗体夹心酶联免疫吸附法 脑脊液 外淋巴液 

分 类 号：R944[医药卫生—药剂学]