Ion-sensitive in-situ gel loaded with rebamipide micelles for the treatment of diabetic keratopathy.

Excessive ROS production triggers diabetic keratopathy (DK), causing dry eyes and impaired healing. Commercial Rebamipide (Reb) eye drops (Mucosta®) suffer from poor bioavailability, short retention, and irritation. To overcome these limitations, this study developed Reb-loaded nanomicelles in ion-sensitive in-situ gels (Reb-NM-ISGs). This dual-approach combines micelles for enhanced solubility and corneal penetration with a gel that forms upon contact with tear fluid, significantly prolonging drug retention. In diabetic models, Reb-NM-ISGs effectively treated dry eye symptoms (improving tear volume, prolonging tear film break time (TBUT)) and corneal injury, accelerating epithelial healing while significantly suppressing key inflammatory cytokines (IL-1β) and alleviating oxidative stress (reducing ROS and MDA, increasing GSH). Safety assessments confirmed good tolerance. Therefore, Reb-NM-ISGs represent a highly promising, safe, and patient-friendly strategy for managing DK, offering a significant advancement over current Reb therapy and providing a valuable reference for diabetic keratopathy research and ocular nanomedicine.