Thermosensitive in situ gels for ocular drug delivery: Advances in polymer-based formulations

Ocular drug delivery presents significant challenges due to the unique anatomical and physiological barriers of the human eye, with the rapid precorneal elimination, limiting the bioavailability of conventional eye drops. Thermosensitive in situ gels have emerged as a promising delivery system to overcome these limitations by undergoing a reversible sol-to-gel transition upon contact with ocular surface temperature, which facilitates ease of administration as a liquid and subsequent transformation into a gel, thereby enhancing precorneal residence time, prolonging the drug release, and improving therapeutic efficacy. This review provides a comprehensive overview of thermos-responsive polymer-based ocular delivery systems, with a specific focus on poloxamers, poly(N-isopropylacrylamide), and cellulose derivatives. Particular attention is given to the physicochemical mechanisms of thermogelation, such as poloxamer micellization and micelle packing, as well as the role of auxiliary polymers in enhancing mucoadhesion, mechanical strength, and gel retention. Additionally, the review synthesizes findings from multiple experimental studies to highlight the critical formulation parameters essential for developing effective in situ gels, including sol-gel transition temperature and time, clarity, rheological behavior, gelling capacity, isotonicity, and ocular biocompatibility. By selecting an optimized thermosensitive in situ gel formulation with suitable characteristics, it becomes possible to develop effective delivery systems targeting both the anterior and posterior segments of the eye.