Overcoming anti-PEG antibody mediated accelerated blood clearance of PEGylated liposomes by pre-infusion with high molecular weight free PEG.

ABSTRACT: Antibodies that specifically bind polyethylene glycol (PEG), i.e. anti-PEG antibodies (APA), are associated with reduced efficacy and increased risk of serious adverse events for several PEGylated therapeutics. Here, we explored the concept of using free PEG molecules to saturate circulating APA. Surprisingly, we found that 40 kDa free PEG effectively restored the prolonged circulation of PEGylated liposomes in the presence of high titers of pre-existing APA for at least 48 h in mice. In contrast, lower molecular weight free PEG (≤10 kDa) failed to restore circulation beyond a few hours. These in vivo results were consistent with estimates from a minimal physiologically based pharmacokinetic model. Importantly, the infusion of free PEG appeared to be safe in mice previously sensitized by i

SUBMITTER: McSweeney MD 

PROVIDER: S-EPMC6874909 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature