Slow intravenous infusion reduces the accelerated blood clearance of PEGylated liposomes by removing anti-PEG antibodies.

Anti-PEG antibodies exist in many individuals and accelerate the clearance of PEGylated liposomes. Herein, we reported that the slow intravenous infusion of PEGylated liposomes significantly reduced their accelerated blood clearance (ABC) phenomenon in rats. This was mainly because the PEGylated liposomes that first entered the bloodstream were sufficient to clear anti-PEG antibodies, thus reducing the clearance of subsequently injected liposomes. In contrast, the rapid intravenous injection of PEGylated liposomes resulted in a uniform binding of anti-PEG antibodies, leading to rapid clearance of PEGylated liposomes from blood circulation. Pretreating PEG-immunized plasma with a low concentration of PEGylated liposomes significantly reduced complement activation-induced drug release. However, the clearance of anti-PEG antibodies did not entirely inhibit the ABC phenomenon of PEGylated liposomes. This might be due to the continuous entry of anti-PEG antibodies into the bloodstream, accelerating the clearance of existing PEGylated liposomes. Our results highlight that the slow infusion of PEGylated liposomes can effectively reduce the ABC phenomenon, which explains why the ABC phenomenon is infrequently observed in clinical applications of DOXIL.