Quercetin for diabetic retinopathy: from molecular targets to targeted delivery strategies

Diabetic retinopathy is a leading cause of preventable vision loss, driven by coupled oxidative, inflammatory, neurodegenerative, and angiogenic injury; current anti-VEGF and laser therapies act mainly on the late vascular stage and leave the upstream injury largely untreated. Quercetin, a dietary flavonol, engages several of these pathogenic nodes at once, but its poor solubility, extensive first-pass metabolism, and the blood-retinal barrier limit retinal exposure.

This review synthesizes the molecular pharmacology of quercetin in diabetic retinopathy, covering Nrf2/HO-1 antioxidant activation, NLRP3/NF-κB anti-inflammation, VEGF-driven anti-angiogenesis, and neurovascular-unit preservation, alongside the nanocarrier strategies (polymeric and lipid nanoparticles, liposomes, and nanoemulsions) and ocular administration routes developed to overcome its bioavailability limits. Literature was identified by structured searches of PubMed, PubMed Central and Web of Science from database inception to August 2026, combining terms for quercetin, diabetic retinopathy, and ocular or nanoparticle drug delivery, with reference lists of retrieved articles screened for additional sources.

Mechanism and delivery have advanced in isolation. We argue that translation requires an integrated 'target-to-delivery' framework that specifies molecular target, disease stage, and carrier-route design together, supported by quantitative retinal-exposure data, standardized models, and formulation-specific clinical testing.