ABSTRACT
Several research groups have shown that anti-polyethylene glycol (anti-PEG) antibodies, produced in response to a first dose of PEGylated liposome, are associated with the rapid clearance of subsequent doses of PEGylated liposomes, which is referred to as the accelerated blood clearance (ABC) phenomenon. Surprisingly, the ABC phenomenon has not been restricted only to PEGylated liposomes. Remarkably, this phenomenon has been recognized upon repeated administration of other PEGylated nanocarriers, including nanoparticles, micelles, and microemulsions and even with PEGylated proteins. Several studies have established the role of the complement system in the accelerated clearance of PEGylated liposomes from systemic circulation. Manipulation of the physicochemical properties of PEGylated nanocarriers, such as particle size, has been used to efficiently alleviate induction of the ABC phenomenon. Among the different strategies employed for abrogating/attenuating the immunogenicity of PEGylated products upon repeated administration, modification of the PEG moiety has received a great deal of attention.
