000161659 001__ 161659
000161659 005__ 20251017144558.0
000161659 0247_ $$2doi$$a10.1080/10717544.2025.2484277
000161659 0248_ $$2sideral$$a144315
000161659 037__ $$aART-2025-144315
000161659 041__ $$aeng
000161659 100__ $$aGonzález-Cela-Casamayor, Ana
000161659 245__ $$aKetorolac, melatonin and latanoprost tri-loaded PLGA microspheres for neuroprotection in glaucoma
000161659 260__ $$c2025
000161659 5060_ $$aAccess copy available to the general public$$fUnrestricted
000161659 5203_ $$aGlaucoma 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.
000161659 536__ $$9info:eu-repo/grantAgreement/ES/AEI/PID2023-148219OB-C21$$9info:eu-repo/grantAgreement/ES/AEI/PID2023-148219OB-C22$$9info:eu-repo/grantAgreement/ES/ISCIII/JR22-00057$$9info:eu-repo/grantAgreement/ES/ISCIII/RD21-0002-0050$$9info:eu-repo/grantAgreement/ES/ISCIII/RD24-0007-0022$$9info:eu-repo/grantAgreement/ES/MICINN/PID2020-113281RB-C21$$9info:eu-repo/grantAgreement/ES/MICINN/PID2020-113281RB-C22
000161659 540__ $$9info:eu-repo/semantics/openAccess$$aby-nc$$uhttps://creativecommons.org/licenses/by-nc/4.0/deed.es
000161659 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000161659 700__ $$aRodrigo, María J.$$uUniversidad de Zaragoza
000161659 700__ $$aMiriam
000161659 700__ $$aBrugnera, Marco
000161659 700__ $$aMunuera, Inés$$uUniversidad de Zaragoza
000161659 700__ $$aMartínez-Rincón, Teresa$$uUniversidad de Zaragoza
000161659 700__ $$aPrats-Lluís, Catalina
000161659 700__ $$aVillacampa, Pilar
000161659 700__ $$aGarcía-Feijoo, Julián
000161659 700__ $$0(orcid)0000-0003-2389-8282$$aPablo, Luis E.$$uUniversidad de Zaragoza
000161659 700__ $$aBravo-Osuna, Irene
000161659 700__ $$0(orcid)0000-0001-6258-2489$$aGarcia-Martin, Elena$$uUniversidad de Zaragoza
000161659 700__ $$aHerrero-Vanrell, Rocío
000161659 7102_ $$11013$$2645$$aUniversidad de Zaragoza$$bDpto. Cirugía$$cÁrea Obstetricia y Ginecología
000161659 7102_ $$11013$$2646$$aUniversidad de Zaragoza$$bDpto. Cirugía$$cÁrea Oftalmología
000161659 773__ $$g32, 1 (2025), 2484277 [22 pp.]$$pDrug deliv.$$tDrug Delivery$$x1071-7544
000161659 8564_ $$s14181000$$uhttps://zaguan.unizar.es/record/161659/files/texto_completo.pdf$$yVersión publicada
000161659 8564_ $$s1221266$$uhttps://zaguan.unizar.es/record/161659/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000161659 909CO $$ooai:zaguan.unizar.es:161659$$particulos$$pdriver
000161659 951__ $$a2025-10-17-14:13:46
000161659 980__ $$aARTICLE