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 hours 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. Our results support further investigation of high molecular weight free PEG as a potential method to control and overcome high titers of APA, restoring the prolonged circulation of PEGylated liposomes and possibly other PEGylated therapeutics.

The dataset uploaded here gives individual mouse-level concentrations of PEGylated liposome doxorubicin (PLD) in blood and organs of elimination. We tested the PK of PLD in naive mice and mice with low (3 ug dose) or high (30 ug dose) APA. We also tested whether administering various sizes of free PEG (10/20/40 kDa) could restore the long-lasting PK of PLD even in mice that received a high dose of APA. The first tab has descriptions of the study conditions tested in each phase (e.g. what size/dose of free PEG was administered to animals in that experiment)