PEG-bottlebrush coatings having reduced antigenicity and methods of using the same
Poly(ethylene glycol) (PEG) is a widely used polymer throughout the medical and pharmaceutical industry. As a so-called stealth polymer, PEG is often used to improve biocompatibility, block immune recognition, prolong pharmacokinetics and reduce biofouling. However, there is a growing concern for the role of anti-PEG immunity in negative outcomes. Anti-PEG antibodies have been found to be associated with poor drug efficacy and can lead to serious anaphylactic reactions. This is concerning because anti-PEG antibodies have been seen in the general population with 37% and 8% showing moderate and high levels respectively. In addition, the FDA now requires testing for anti-PEG antibodies before treatment with experimental PEGylated compounds. Therefore, there is an essential need for new and improved stealth polymers with decreased immunogenicity.
This invention is for PEG assembled in “bottlebrush” configurations on planar surfaces that maintains stealth properties and low antigenicity. By altering ethylene glycol (EG) repeat lengths of the bottlebrush sidechains the inventors identified coatings having sidechain lengths of two and three EG repeats as the optimal configurations. They demonstrated the utility of this coating when applied to immunoassays and showed that were non-reactive toward anti-PEG antibodies. They also showed that this coating was resistant toward both toward both backbone derived and endgroup-reactive anti-PEG antibodies, allowing for the use of methoxy-capped PEG sidechains. Finally, the bottle brush coating was shown to be resistant against anti-PEG antibody positive clinical plasma samples. This work identifies how PEG bottlebrushes can be used to assemble three-dimensional surfaces while maintaining stealth properties and has great potential for the use in bio-interfacing clinical devices.
- Maintains stealth properties
- Low antigenicity
- PEG derived