PEG with a lower molecular weight is less likely to elicit an IgM reaction. In preclinical models, substitute polymers such as polysarcosine for PEG prevent ABC reactions. Complement activation can also be reduced by altering the liposome’s composition, such as by adding more cholesterol. Another strategy is to use an extracorporeal immunoadsorption device with PEGylated particles to collect IgM and selectively deplete anti-PEG IgM. The immunoadsorber was administered to CARPA-sensitive pigs in a test to determine its safety and effectiveness. The results showed a 90% reduction in anti-PEG IgM levels and the ability to administer PEGylated liposomes repeatedly without causing pseudoallergy reactions.
To summarize, the clinical translation of nanomedicines such as PEGylated liposomes is hampered by IgM-mediated pseudoallergy. Engineering techniques to lower this risk of hypersensitivity have been guided by the elucidation of the molecular pathways involving complement activation and anti-PEG IgM. Safe, recurrent administration of medications using nanoparticles may be made possible by further developments to decrease IgM reactions or specifically eliminate anti-PEG IgM. Further comprehension of the pathways leading to pseudoallergy may potentially clarify other inexplicable infusion reactions to pegylated biopharmaceuticals.
