Dual Stimuli Responsive In-situ Hydrogels for Ocular Drug Delivery: Recent Advances, Challenges and Future Perspectives

Abstract

Because of the special anatomical and physiological barriers of the eye, such as nasolacrimal drainage, fast tear turnover, and restricted corneal permeability, which together lower the bioavailability of traditional ophthalmic formulations, ocular medication delivery is still a major issue. Because in-situ hydrogels can undergo a sol-to-gel transition in response to physiological stimuli, extending precorneal residence time and improving therapeutic efficacy, they have become viable drug delivery platforms. Because they react to two physiological triggers, such as pH, temperature, or ionic strength, dual stimuli-responsive in- situ hydrogels have drawn a lot of attention among these systems. This allows for better gelation control and more accurate drug release than single stimulus-responsive systems.
This article offers a thorough overview of dual stimuli-responsive in-situ hydrogels for ocular drug delivery, emphasizing their formulation techniques, polymeric components, design concepts, mechanisms of responsiveness, and assessment parameters. A critical discussion is given of recent developments in the use of these systems to treat ocular conditions such as corneal inflammation, bacterial infections, dry eye syndrome, glaucoma, and allergic conjunctivitis. The benefits of dual-responsive hydrogels are emphasized, including increased ocular retention, better bioavailability, prolonged drug release, and less burst release. Key elements affecting formulation performance and drug release behavior are also investigated.
Polymer compatibility, drug stability, ocular discomfort, tear fluid composition variability, sterilizing requirements, manufacturing scale-up, and regulatory approval are some of the obstacles that still need to be overcome despite their promising promise. Dual-responsive ocular hydrogel systems' clinical translation and commercialization are still hampered by these restrictions.
Future studies are anticipated to concentrate on the creation of sophisticated smart hydrogels, customized eye treatments, AI-assisted formulation design, 3D-printed hydrogel systems, biomimetic and bioadhesive materials, and gene and protein delivery platforms. Dual stimuli-responsive in-situ hydrogels are expected to be a key component of the future generation of ocular drug delivery systems, providing safer, more efficient, and patient-centered therapeutic options, as biomaterials research and pharmaceutical technology continue to progress.

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