González-Cela Casamayor, Miriam AnaRodrigo Sanjuán, Maria JesúsBrugnera, MarcoMunuera, InésMartínez Rincón, TeresaPrats Lluís, CatalinaVillacampa, PilarGarcía Feijoo, JulianPablo-Júlvez, Luis E.Bravo Osuna, IreneGarcía Martñin, ElenaHerrero Vanrell, Rocío2025-06-302025-06-302025-04-111521-0464https://hdl.handle.net/2445/221890Glaucoma 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 mu m particle size and drug content (mu g/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.22 p.application/pdfengcc-by-nc (c) González-Cela Casamayor et al., 2025http://creativecommons.org/licenses/by-nc/3.0/es/MelatoninaGlaucomaTerapèutica oftalmològicaMelatoninGlaucomaOphthalmological therapeuticsinfo:eu-repo/semantics/article2025-06-10info:eu-repo/semantics/openAccess40211987