Recent advances in thermo-responsive hydrogels for ocular drug delivery: Materials, mechanisms, and clinical potential

Recent advancements in thermo-responsive hydrogels have revolutionized ocular drug delivery by offering a smart, non-invasive, and patient-compliant platform for sustained and targeted therapy. This review comprehensively discusses the development and application of thermo-responsive hydrogels in the treatment of prevalent ocular diseases such as dry eye syndrome, glaucoma, and uveitis. These hydrogels undergo sol-to-gel transitions at physiological temperatures, enabling in situ gelation upon ocular administration. The underlying mechanism enhances drug residence time and enables controlled drug release at the site of action. Formulations leverage both natural polymers such as chitosan, gelatin, and hyaluronic acid and synthetic polymers like poloxamers, PNIPAM, and PEG-based systems, each contributing to biocompatibility, biodegradability, and responsiveness to temperature stimuli. Key properties such as temperature-sensitive phase transition, controlled drug release, and high biocompatibility position these hydrogels as superior alternatives to conventional eye drops. The benefits include reduced dosing frequency, minimized systemic absorption, and enhanced drug bioavailability. Recent innovations focus on sustainable hydrogel synthesis, incorporation of novel polymer composites, and improved drug encapsulation techniques. Despite significant progress, challenges remain, including potential cytotoxicity of synthetic components, scalability of production, and achieving precise drug release kinetics. Future directions aim to optimize formulation stability, explore stimuli-combination responsive systems, and integrate nanotechnology for precision medicine. This review underscores the transformative potential of thermo-responsive hydrogels in ocular therapeutics and highlights their promise as a cornerstone in the next generation of smart ophthalmic drug delivery systems.