Injectable Thermoresponsive Hydrogels for Localized Drug Delivery: Mechanisms, In Vivo Evidence and Translational Challenges

Abstract

Injectable thermoresponsive hydrogels are useful for localized drug delivery because they can be administered as low-viscosity formulations and then form, or reinforce, therapeutic depots directly at diseased tissue sites. Their common design principle is a temperature-dependent transition from a flowable formulation before administration to an in situ matrix at physiological temperature, or a thermally regulated change in swelling, mesh size, drug-matrix affinity or degradation. This review focuses on thermoresponsive injectable systems for localized delivery, including PNIPAM-based systems, poloxamers/Pluronics, PEG/polyester block copolymers, polyurethane-based hydrogels, chitosan-based thermogels, hyaluronan- and glycosaminoglycan-based systems, and selected multicomponent or nanocomposite networks. The in vivo application areas considered are local cancer therapy, wound healing and antibacterial treatment, osteoarthritis and intra-articular delivery, and myocardial infarction/cardiac repair. Across these indications, preclinical studies suggest that thermoresponsive hydrogels may prolong local residence time, reduce systemic exposure, enhance delivery of poorly soluble or unstable payloads, and modulate disease-specific microenvironments. Remaining challenges include gelation control, mechanical stability, degradation products, immune response, sterilization, manufacturing reproducibility, disease heterogeneity and robust translational validation.