Abstract
Zwitterionic polymers, ampholytic macromolecules containing ionic moieties of opposite sign on the same pendant groups, exhibit strong protein-repulsive properties and an inherent biological inertness. For that reason, these highly hydrated inner salt macromolecules have emerged as some of the most viable alternatives to poly(ethylene glycol) (PEG), a gold standard in enabling stealth behavior in life science applications. However, the structural diversity of polymer zwitterions remains limited, and currently available macromolecules do not possess an intrinsic ability to undergo hydrolytical degradation, an important prerequisite for use in drug delivery applications. The present paper reports on the synthesis of a zwitterionic polymer, a multimerized form (two thousand copies), of a biologically benign buffering agent, HEPES, which is covalently assembled on a polyphosphazene backbone. The polymer exhibits typical polyzwitterionic solution behavior, an environmentally dependent hydrolytic degradation pattern, and excellent in vitro compatibility, features that highlight its potential utility for life science applications.