Polymeric nanoparticles augment the ocular hypotensive effect of melatonin in rabbits

Melatonin, a neurohormone secreted by the pineal gland, is able to modulate intraocular pressure (IOP). The aim of this study was to generate nanoparticle (NPs) sustained release formulations that allow to extend the pre-corneal residence time of melatonin, thus prolonging its pharmacological effects. Poly(D,L-lactide-co-glycolide) (PLGA) and PLGA-poly(ethylenglycole) (PEG) nanoparticles (NPs) were used to prepare the new melatonin formulations. Mean particle diameter and zeta potential, determined after freeze-drying in the presence of glucose as a cryoprotectant, ranged between 100 and 400 nm and -32.2/-8.2 mV, respectively for PLGA and PLGA-PEG NPs. Melatonin loading ranged between 44% and 80%. DSC analysis showed a homogeneous molecular dispersion of the drug in the NPs matrix. The hypotensive effect was evaluated by measuring IOP during 24h after instillation in the rabbit eye, in comparison with a melatonin aqueous solution at the same concentration (0.08%, w/v). The tested NPs showed good ocular tolerability in rabbit eye using biomicroscopy. Melatonin-loaded PLGA-PEG NPs were the most effective in reducing IOP up to 8h (maximum IOP reduction: 5 mmHg)