Applications of Thermoresponsive Hydrogels for Sustained Drug Release in Ocular and Intravitreal Formulations...

Vision loss is one of the most debilitating eye impairments, with the leading causes such as cataracts, glaucoma, injuries to the surface of the eye and age-related macular degeneration, significantly affecting a person's quality of life and placing a substantial burden on healthcare systems. Effective treatment of these conditions remains challenging due to the complex anatomical and physiological barriers of the eye, which limit the penetration and retention of topically and intravitreally administered drugs. As a result, conventional ocular therapies often exhibit poor therapeutic efficacy, low bioavailability, necessitating frequent administration, reducing patient compliance, and increasing the risk of treatment-related complications. Thermoresponsive hydrogels have emerged as a promising class of in situ-forming drug delivery systems that utilize physiological temperature as a trigger to transition from a sol to a gel state upon administration. This sol-gel transition enhances precorneal or intraocular residence time, improves mucoadhesion, and facilitates sustained drug release. These characteristics make thermoresponsive hydrogels particularly suitable for ocular and intravitreal formulations targeting both anterior and posterior-segment diseases. Thermoresponsive polymers may exhibit lower critical solution temperature (LCST), upper critical solution temperature (UCST), or combined LCST-UCST phase behavior depending on polymer composition, enabling tunable gelation properties to control rate of drug release profiles. This review provides an overview of recent developments in thermoresponsive hydrogels for ophthalmic drug delivery, including emerging dual-responsive systems, with emphasis on gelation mechanisms, drug-release kinetics, and therapeutic applications in anterior and posterior-segment diseases. Key translational considerations, including formulation stability, sterilization, scalability, and regulatory challenges, are also discussed. In addition, the article highlights future research directions to support the continued application and clinical translation of thermoresponsive hydrogel-based ocular drug delivery systems.