Biodegradable zwitterionic polymers as PEG alternatives for drug delivery

Poly(ethylene glycol) (PEG) is a highly biocompatible and water-soluble polymer that is widely utilized for biomedical applications. Unfortunately, the immunogenicity and antigenicity of PEG severely restrict the biomedical efficacy of pegylated therapeutics. As emerging PEG alternatives, biodegradable zwitterionic polymers (ZPs) have attracted significant interest in recent years. Biodegradable ZPs generally are not only water-soluble and immunologically inert, but also possess a range of favorable biomedically relevant properties, without causing long-term side effects for in vivo biomedical applications. This review presents a systematic overview of recent studies on biodegradable ZPs. Their structural designs and synthetic strategies by integrating biodegradable base polymers with zwitterions are addressed. Their applications in the delivery of small molecule drugs (as mono-drugs or multi-drugs) and proteins are highlighted.