161659 20251017144558.0 doi 10.1080/10717544.2025.2484277 sideral 144315 ART-2025-144315 eng González-Cela-Casamayor, Ana Ketorolac, melatonin and latanoprost tri-loaded PLGA microspheres for neuroprotection in glaucoma 2025 Access copy available to the general public Unrestricted 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. info:eu-repo/grantAgreement/ES/AEI/PID2023-148219OB-C21 info:eu-repo/grantAgreement/ES/AEI/PID2023-148219OB-C22 info:eu-repo/grantAgreement/ES/ISCIII/JR22-00057 info:eu-repo/grantAgreement/ES/ISCIII/RD21-0002-0050 info:eu-repo/grantAgreement/ES/ISCIII/RD24-0007-0022 info:eu-repo/grantAgreement/ES/MICINN/PID2020-113281RB-C21 info:eu-repo/grantAgreement/ES/MICINN/PID2020-113281RB-C22 info:eu-repo/semantics/openAccess by-nc https://creativecommons.org/licenses/by-nc/4.0/deed.es info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Rodrigo, María J. Universidad de Zaragoza Miriam Brugnera, Marco Munuera, Inés Universidad de Zaragoza Martínez-Rincón, Teresa Universidad de Zaragoza Prats-Lluís, Catalina Villacampa, Pilar García-Feijoo, Julián Pablo, Luis E. Universidad de Zaragoza (orcid)0000-0003-2389-8282 Bravo-Osuna, Irene Garcia-Martin, Elena Universidad de Zaragoza (orcid)0000-0001-6258-2489 Herrero-Vanrell, Rocío 1013 645 Universidad de Zaragoza Dpto. Cirugía Área Obstetricia y Ginecología 1013 646 Universidad de Zaragoza Dpto. Cirugía Área Oftalmología 32, 1 (2025), 2484277 [22 pp.] Drug deliv. Drug Delivery 1071-7544 14181000 http://zaguan.unizar.es/record/161659/files/texto_completo.pdf Versión publicada 1221266 http://zaguan.unizar.es/record/161659/files/texto_completo.jpg?subformat=icon icon Versión publicada oai:zaguan.unizar.es:161659 articulos driver 2025-10-17-14:13:46 ARTICLE