Nanoformulations for Ocular Drug Delivery in Glaucoma: From Metal-Based Nanoparticles to Advanced Nanocarriers.

Glaucoma is a chronic and progressive optic neuropathy in which sustained intraocular pressure (IOP) reduction remains the main therapeutic objective, while increasing attention is being directed toward neuroprotective strategies and improved ocular drug delivery. Conventional topical therapies are frequently limited by short precorneal residence time, poor ocular bioavailability, and the need for frequent administration. This narrative review examines nanoformulation-based strategies investigated for ocular drug delivery in glaucoma, ranging from metal-based nanoparticles, including gold, silver, zinc-, copper-, and iron-based systems, to advanced nanocarriers such as liposomes, polymeric nanoparticles, solid lipid nanoparticles, nanostructured lipid carriers, nanoemulsions, nanosuspensions, dendrimers, cyclodextrin-based systems, and hydrogels. Particular attention is given to the relationship between nanocarrier composition, physicochemical characteristics, drug-loading and release properties, ocular retention and penetration, therapeutic effects, and the level of experimental evidence. The review further compares metal-based nanoparticles with non-metal-based nanocarriers, highlighting their respective advantages and limitations in terms of drug delivery, sustained ocular exposure, therapeutic potential, biocompatibility, toxicity, and translational relevance. Although several nanoformulation platforms have demonstrated promising results in preclinical studies, the available evidence remains heterogeneous and predominantly preclinical. Further research is needed to establish long-term ocular safety, optimize formulation characteristics, standardize evaluation methods, and determine the clinical relevance of these emerging delivery systems.