%0 Journal Article
%A Rodrigo, María J
%A Brugnera, Marco
%A Munuera, Ines
%A Martínez-Rincón, Teresa
%A Prats-Lluís, Catalina
%A Villacampa, Pilar
%A García Feijoo, Julián
%A Pablo, Luis E
%A Bravo Osuna, Irene
%A Garcia-Martin, Elena
%A Herrero Vanrell, María Del Rocío
%A González-Cela Casamayor, Miriam Ana
%T Ketorolac, melatonin and latanoprost tri-loaded PLGA microspheres for neuroprotection in glaucoma
%D 2025
%U https://hdl.handle.net/20.500.14352/128302
%X Glaucoma is a multifactorial neurodegenerative disease that affects the retina and optic nerve. The aim of this work was to reach different therapeutics targets by co-encapsulating three neuroprotective substances with hypotensive (latanoprost), antioxidant (melatonin) and anti-inflammatory (ketorolac) activity in biodegradable poly (lactic-co-glycolic acid) (PLGA) microspheres (MSs) capable of releasing the drugs for months after intravitreal injection, avoiding the need for repeated administrations. Multi-loaded PLGA MSs were prepared using the oil-in-water emulsion solvent extraction-evaporation technique and physicochemically characterized. PLGA 85:15 was the polymer ratio selected for the selected formulation. Tri-loaded MSs including vitamin E as additive showed good tolerance in retinal pigment epithelium cells after 24 h exposure (>90% cell viability). The final formulation (KMLVE) resulted in 33.58 ± 5.44 µm particle size and drug content (µg/mg MSs) of 39.70 ± 5.89, 67.28 ± 4.17 and 7.51 ± 0.58 for melatonin, ketorolac and latanoprost respectively. KMLVE were able to release in a sustained manner the three drugs over 70 days. KMLVE were injected at 2 and 12 weeks in Long-Evans rats (n = 20) after the induction of chronic glaucoma. Ophthalmological tests were performed and compared to not treated glaucomatous (n = 45) and healthy (n = 17) animals. Treated glaucomatous rats reached the lowest intraocular pressure, enhanced functionality of bipolar and retinal ganglion cells and showed greater neuroretinal thickness by optical coherence tomography (p < 0.05) compared to not treated glaucomatous rats at 24 weeks follow-up. According to the results, the tri-loaded microspheres can be considered as promising controlled-release system for the treatment of glaucoma.
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