F127-CHO/Gelatin-NH₂ hydrogel delivering liposomal eriodictyol suppresses ferroptosis and attenuates retinal ganglion cell loss

Glaucoma is an irreversible blinding eye disease characterized by the loss of retinal ganglion cells (RGCs), posing a significant threat to human visual health. Currently available, clinical treatments for glaucoma cannot completely suppress the progression of RGC death in glaucoma. Eriodictyol (Eri) has been shown to possess various biological activities, including anti-inflammatory, antioxidant, and neuroprotective effects. However, its low water solubility and bioavailability hinder its clinical application. To address these challenges, we developed a ROS-responsive liposome (Lip@Eri) embedded within an F127-CHO/Gel-NH₂ hydrogel (FG/Lip@Eri) for intraocular delivery of Eri, and further evaluated its ability to suppress ferroptosis and mitigate RGC loss. This drug delivery system enhanced the bioavailability of Eri and demonstrated excellent biocompatibility. In vitro, Lip@Eri inhibited glutamate-induced ferroptosis in R28 cells by reducing iron accumulation and lipid peroxidation, associated with PI3K–AKT pathway activation. Further in vivo experiments demonstrated that FG/Lip@Eri effectively suppresses ferroptosis, protects RGCs, and preserves visual function. Therefore, FG/Lip@Eri may represent a novel strategy for neuroprotection in glaucoma.