Effects of complement inhibition on the ABC phenomenon in rats

作     者：Lirong Wang Yuqing Su Xuling Wang Kaifan Liang Mengyang Liu Wenya Tang Yanzhi Song Xinrong Liu Yihui Deng 

作者机构：Shenyang Pharmaceutical University 

出 版 物：《Asian Journal of Pharmaceutical Sciences》 (亚洲药物制剂科学（英文）)

年 卷 期：2017年第12卷第3期

页      面：250-258页

核心收录：

学科分类：1007[医学-药学(可授医学、理学学位)] 1006[医学-中西医结合] 100706[医学-药理学] 1002[医学-临床医学] 100602[医学-中西医结合临床] 10[医学] 

基　　金：supported by the National Natural Science Foundation of China(Grant No.81373334) 

主　　题：ABC phenomenon PEGylated nanoemulsions Complement inhibition Cobra venom factor 

摘      要：Researchers reported that intravenously injected PEGylated colloidal drug carriers lose their long-circulating characteristic and accumulated extensively in liver when they are administrated twice in the same animal with certain intervals. This phenomenon was referred to as the accelerated blood clearance(ABC) phenomenon . Some former studies had found that complement-mediated phagocytosis, activated by antigen–antibody complex, was responsible for inducing the phenomenon. According to the theory, we have used cobra venom factor to deplete complement in vivo and to investigate the effect of complement inhibition on the ABC phenomenon. Rats were administered by injection of cobra venom factor solution to build up the model of complement exhaustion/inhibition, and the effect of the inhibition of complement on ABC phenomenon was carried out. It seemed that inhibition of complement didn’t affect the pharmacokinetic of the first infection. By contrast, in rats of which complement had been depleted, the second dose of PEGylated nanoemulsions showed enhanced circulation time compared with normal rats in a complement inhibition-independent manner, but the ABC phenomenon was not completely eliminated. It indicated that complement inhibition could certainly weaken the accelerated clearance;meanwhile, there were other factors causing the ABC *** findings provide novel insights into the attenuating of ABC phenomenon and lay foundation for further study of immune mechanism.