Effects of complement inhibition on the ABC phenomenon in rats

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 effect.These findings provide novel insights into the attenuating of ABC phenomenon and lay foundation for further study of immune mechanism.

The accelerated blood clearance phenomenon of PEGylated nanoemulsion upon cross administration with nanoemulsions modified with polyglycerin

For investigating the accelerated blood clearance(ABC) phenomenon of polyglycerin modified nanoemulsions upon cross administration with polyethylene glycol(PEG) covered nanoemulsion, we used the 1,2-distea-royl-sn-glycero-3-phosphoethanolamine-npolyglycerine-610 and the 1,2-distearoyl-n-glycero-3-phosphoethanolamine-n-[methoxy(polyethylene glycol)-2000] as modify materials, the dialkylcarbocyanines as fluorescence indicator. Exhausted macrophages rat model was established and new material containing polycarboxyl structure was synthesized. The microplate reader and the in vivo optical imaging system were applied to measure the concentration of nanoemulsions in tissues.The results show that the first dose of polyglycerin modified nanoemulsion can induce the ABC phenomenon of the second dose of PEGylated nanoemulsion. With the increase in the amount of the surface polyglycerin, the extent of the ABC phenomenon decreases. Liver accumulation has positive relationship with the ABC phenomenon. Furthermore, kupffer cells in liver can get more immune information from polyhydroxy structure than polycarboxyl group in the modify compound. The results of our work imply that the polycarboxyl structure has advantages to eliminate the ABC phenomenon.