PMPCylated liposomes in drug delivery and beyond.

Poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) is a zwitterionic polymer that mimics phosphatidylcholine headgroups of cell membrane, exhibiting excellent biocompatibility and antifouling properties. Recently, PMPCylated liposomes, i.e., liposomes functionalized with PMPC chains, have emerged as promising nanocarrier for drug delivery and other biomedical applications. This review summarizes recent progress in the design and application of PMPCylated liposomes, with a focus on their roles in prolonging systemic circulation, enhancing immune evasion, improving boundary lubrication for joint therapy, and overcoming biological barriers such as mucus and BBB. PMPC coatings outperform traditional PEGylation (polyethylene glycol, PEG) by more effectively minimizing protein adsorption, avoiding immune recognition, and enabling repeatable administration without accelerated clearance. Intra-articular PMPCylated liposomes exhibit superlubrication and cartilage adherence, offering both mechanical protection and therapeutic potential in osteoarthritis. In parallel, the hydration layer formed by PMPC facilitates mucus penetration and biofilm disruption, expanding its utility in oral, infectious, and neurological drug delivery. Finally, the clinical translational potential and future design strategies are discussed. Together, these findings highlight PMPCylated liposomes as a versatile and promising platform for drug delivery and beyond.