Dual-functional nanoparticle formulations for simultaneous intraocular pressure reduction and neuroprotection in glaucoma: a review.

Glaucoma is a leading cause of irreversible blindness, driven by elevated intraocular pressure (IOP), progressive retinal ganglion cell (RGC) loss, and optic nerve degeneration. Current therapies rely on lowering IOP, which slows but does not halt disease progression. Dual-functional nanoparticle (NP) formulations represent a promising approach to simultaneously address these therapeutic targets. By improving ocular drug penetration, sustaining release, and enabling co-delivery of diverse agents, nanocarriers can achieve prolonged IOP reduction while directly preserving RGC and optic nerve against excitotoxicity, oxidative stress, inflammation, etc. In this work, we reviewed the glaucoma pathophysiology and the rationale for dual therapy. We then discussed major classes of NP systems and strategies that can fulfill dual-function therapy. The preclinical studies and early clinical developments were also highlighted. We also discussed the challenges of formulation stability, safety, and regulatory approval, and outlined future directions. Together, these advances position dual-functional NP systems as a transformative strategy for disease-modifying glaucoma therapy, bridging the gap between IOP control and neuroprotection to preserve vision.