Development of a Sustainable In Situ Gel System for Ocular Delivery of p-Coumaric Acid for Corneal Wound Healing

Corneal injuries are a leading cause of vision impairment, yet current therapies provide limited benefit due to poor ocular bioavailability and rapid drug clearance. To address this challenge, we developed a pH-sensitive in situ gel of p-coumaric acid (pCA) for sustained ocular delivery and enhanced wound healing. In vitro studies on SIRC cells identified 80 μg/mL pCA as a safe and effective concentration for supporting viability and migration. The optimized gel, formulated with Carbopol 940 and HPMC K100 M using central composite design, exhibited rapid gelation at ocular pH, pseudoplastic rheology, suitable zeta potential, and high entrapment efficiency (85.95%). FESEM confirmed pH-triggered sol-gel transition, while in vitro release demonstrated sustained delivery for 12 h (92.62% cumulative release). Safety was verified through RBC lysis, CAM, goat corneal histology, and rabbit eye irritation tests, all showing no adverse effects. In vivo evaluation in a rat corneal alkali burn model confirmed accelerated wound healing. This system offers a safe, biocompatible, and effective ocular therapy for corneal wounds.