Physicochemical and safety evaluation of an antioxidant ophthalmic hydrogel for corneal injuries

Corneal injuries are frequently associated with oxidative stress and standard treatment are only to prevent infection, reduce pain and inflammation. This work describes the development of antioxidant ophthalmic hydrogels containing Idebenone (IDB) and hydroxocobalamin (HCB) as a complement treatment for corneal injuries, using hydroxypropyl- β-cyclodextrin (HPβCD) to improve IDB aqueous solubility. Three hydrogels were prepared (hyaluronic acid, FAH; poloxamer 407, FP; and polyvinyl alcohol, FPVA) and characterized for physicochemical properties, mucoadhesion and safety. Phase-solubility assays supported 1:1 inclusion complex formation and achieved to solubilize a high IDB load. FP displayed thermogelling properties rheologically, showing increased viscosity between room and physiological temperatures. In vitro release in Franz cells indicated sustained delivery for both actives, best described by the Korsmeyer-Peppas model. Ex vivo bovine corneal permeation showed no detectable transcorneal diffusion of drugs, consistent with a local action on superficial corneal layers. FP exhibited suitable wettability on corneal surface and was selected for further evaluation. Antioxidant capacity assessed by FRAP demonstrated high activity for FP compared with conventional artificial tears based on HPMC or Hypromellose. Ocular safety was supported by BCOP and HET-CAM assays, showing no relevant impairment of corneal integrity or irritation, and cytotoxicity assays in human corneal epithelial cells and keratocytes showed the safety of the treatment. Additionally, C. Elegans survival assay confirmed the treatment́s safety. Overall, the developed hydrogel, composed of P407 and HPβCD, shows potential as a safe topical platform to increase ocular residence time and provide localized antioxidant support during corneal injuries management.