Engineering poloxamer copolymers for in situ gelling systems: Structural, compositional, and functional modifications

Poly(ethylene oxide) (PEO) and poly(propylene oxide) (PPO), organized in PEO_X-PPO_Y-PEO_X configuration, constitute the family of amphiphilic triblock copolymers known as poloxamers, which serve as highly promising temperature-responsive in situ gelling platforms for effective drug delivery. Since poloxamer-based systems remain liquid at room temperature, they can potentially be administered with greater convenience. When exposed to increased temperatures, their unique thermoresponsive behavior induces micellar self-assembly, followed by sol-to-gel transition at physiological temperatures, enabling sustained drug release. However, the application of poloxamers for hydrogel systems has been primarily restricted by their insufficient mechanical properties and an interconnected aqueous structure, which accelerates gel erosion and drug diffusion. The nature, composition, and concentration of poloxamer copolymer serve among the most substantial functions in determining the degree of drug diffusion from the in situ gelling matrix. Focusing on prolonging drug release, enhancing residence time at the administration site, and inducing stimuli-responsive properties to poloxamer-based gels, numerous studies have explored modifying gel characteristics through physical blending or chemical crosslinking with additives, as well as chemical functionalization of poloxamers, depending on desired therapeutic application. This review explores the significant structural and compositional aspects of poloxamer copolymers, along with the strategic molecular modifications aimed at improving their physicochemical properties.