Zwitterion-Based Polymeric Carriers for Efficient Drug Delivery across Biological Barriers

Polymeric carriers, by virtue of their tunable physicochemical properties, serve as critical platforms for drug delivery. To enhance therapeutic efficacy, considerable effort has been devoted to functionalizing polymeric carriers and exploring alternative routes of administration. However, regardless of the administration modality, polymeric carriers must overcome multiple physiological barriers during delivery. In this context, zwitterionic-rich polymeric carriers exhibit superior penetration across physiological barriers, attributable to their remarkable hydration capacity and resistance to protein adsorption. Understanding how the zwitterion structure governs barrier penetration is critical for designing drug delivery systems with enhanced tissue targeting. This review summarizes the design strategies of zwitterion-based polymeric carriers, focusing on their structure–activity relationships and mechanisms for overcoming specific physiological barriers via different administration routes. Finally, we provide perspectives on harnessing artificial intelligence for the intelligent design of zwitterion-based polymeric carriers toward their accelerated clinical translation.