Nano formulations of quercetin for ocular delivery

Quercetin (QUE), a bioactive flavonoid with potent antioxidant, anti‑inflammatory, and neuroprotective properties, has emerged as a promising therapeutic candidate for age‑related macular degeneration, diabetic retinopathy, cataracts, glaucoma, dry eye disease, and allergic conjunctivitis. Its therapeutic effects are primarily mediated through modulation of key molecular pathways, including direct scavenging of reactive oxygen species (ROS), activation of Nrf2‑dependent antioxidant responses, inhibition of NF‑κB and MAPK signaling, and downregulation of pro‑inflammatory cytokines and angiogenic mediators such as VEGF. However, effective ocular delivery of QUE remains challenging because anatomical and physiological barriers severely limit drug penetration and retention, and because QUE itself exhibits poor aqueous solubility, chemical instability, rapid clearance, and a narrow therapeutic window at the tissue level. Recent advances in nanotechnology‑based delivery systems including liposomes, solid lipid nanoparticles, nanostructured lipid carriers, nanoemulsions, micelles, and polymeric nanoparticles have shown considerable potential to enhance corneal and scleral permeability, prolong ocular residence time, improve QUE stability and bioavailability, and enable more controlled local exposure. This review critically evaluates recent progress in QUE‑loaded nanocarriers for ocular drug delivery, integrating mechanistic insights, formulation strategies, and preclinical and emerging clinical data, and discusses key challenges and opportunities for the safe and effective clinical translation of quercetin‑based ocular nanotherapeutics.