Development of a Sustainable <i>In Situ</i> Gel System for Ocular Delivery of <i>p</i> -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 <i>in situ</i> gel of <i>p</i>-coumaric acid (pCA) for sustained ocular delivery and enhanced wound healing. <i>In vitro</i> 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 <i>in vitro</i> 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. <i>In vivo</i> 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.