Development of hyaluronic acid-based nanocomposite eye drops: A synergistic platform for enhanced ocular delivery of acetazolamide

This study developed hyaluronic acid-based nanocomposite eye drops for topical ocular delivery of acetazolamide as a potential glaucoma treatment. Acetazolamide nanocrystals were incorporated into hyaluronic acid hydrogels to create formulations with improved colloidal stability, acceptable ophthalmic pH and osmolarity, pseudoplastic flow behaviour, enhanced mucoadhesion, and sustained drug release. The optimized formulation contained hyaluronic acid 1.25% w/v and acetazolamide nanocrystals 5% w/v, preserving nanocrystal integrity while improving dispersion stability relative to aqueous nanosuspensions. In vitro release showed a biphasic profile with an initial burst followed by prolonged diffusion-controlled release, while in vivo rabbit studies showed no irritation or ocular damage after instillation. The optimized nanocomposite hydrogel produced a significant and prolonged reduction in intraocular pressure compared with normal saline and tended to outperform the commercial brinzolamide reference, while using a lower acetazolamide dose than prior nanocrystal-only formulations. Overall, the paper presents a synergistic ocular drug delivery platform that combines nanocrystal-enhanced drug availability with hydrogel-mediated retention and mucoadhesion.