An enhanced-permeability amphiphilic nanogel loaded with sulforaphane for synergistic anti-oxidative and anti-ferroptotic therapy of corneal alkali burn.

BACKGROUND: Alkali-induced ocular injury is a severe blinding disease where oxidative stress and ferroptosis drive corneal neovascularization and fibrosis. The natural compound sulforaphane (SFN) can inhibit these processes but its efficacy is limited by poor solubility, inadequate corneal penetration, and short ocular retention. METHODS: SFN-loaded liposomes (LPS) were prepared and incorporated into a poloxamer-based thermosensitive hydrogel (HP@LPS). Its gelation properties at ocular surface temperature and in vitro release were characterized. The antioxidant and anti-ferroptosis effects of LPS were evaluated in vitro, while therapeutic efficacy of HP@LPS in inhibiting neovascularization, fibrosis, and promoting corneal repair was assessed in a rat alkali burn model. RESULTS: HP@LPS was successfully developed, undergoing in situ gelation for sustained SFN release, with LPS ensuring efficient corneal penetration. In vitro, LPS attenuated oxidative stress and lipid peroxidation, upregulated ferroptosis-inhibitory proteins, and suppressed neovascularization and fibrosis. In vivo, HP@LPS ameliorated inflammation, neovascularization, and fibrosis through synergistic antioxidative and anti-ferroptotic mechanisms, with favorable bioavailability and minimal toxicity. CONCLUSIONS: HP@LPS enhanced corneal retention and stromal penetration of SFN, promoting corneal repair and regeneration. This system offers a novel therapeutic strategy for corneal alkali burn and represents a promising candidate for clinical translation.