Ketorolac, melatonin and latanoprost tri-loaded PLGA microspheres for neuroprotection in glaucoma
González-Cela-Casamayor, Ana ; 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) ; Bravo-Osuna, Irene ; Garcia-Martin, Elena (Universidad de Zaragoza) ; Herrero-Vanrell, Rocío
Resumen: 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.
Idioma: Inglés
DOI: 10.1080/10717544.2025.2484277
Año: 2025
Publicado en: Drug Delivery 32, 1 (2025), 2484277 [22 pp.]
ISSN: 1071-7544
Financiación: info:eu-repo/grantAgreement/ES/AEI/PID2023-148219OB-C21
Financiación: info:eu-repo/grantAgreement/ES/AEI/PID2023-148219OB-C22
Financiación: info:eu-repo/grantAgreement/ES/ISCIII/JR22-00057
Financiación: info:eu-repo/grantAgreement/ES/ISCIII/RD21-0002-0050
Financiación: info:eu-repo/grantAgreement/ES/ISCIII/RD24-0007-0022
Financiación: info:eu-repo/grantAgreement/ES/MICINN/PID2020-113281RB-C21
Financiación: info:eu-repo/grantAgreement/ES/MICINN/PID2020-113281RB-C22
Tipo y forma: Article (Published version)
Área (Departamento): Área Obstetricia y Ginecología (Dpto. Cirugía)
Área (Departamento): Área Oftalmología (Dpto. Cirugía)
You must give appropriate credit, provide a link to the license, and indicate if changes were made. You may do so in any reasonable manner, but not in any way that suggests the licensor endorses you or your use. You may not use the material for commercial purposes.
Exportado de SIDERAL (2025-06-16-09:07:35)
Visitas y descargas
Idioma: Inglés
DOI: 10.1080/10717544.2025.2484277
Año: 2025
Publicado en: Drug Delivery 32, 1 (2025), 2484277 [22 pp.]
ISSN: 1071-7544
Financiación: info:eu-repo/grantAgreement/ES/AEI/PID2023-148219OB-C21
Financiación: info:eu-repo/grantAgreement/ES/AEI/PID2023-148219OB-C22
Financiación: info:eu-repo/grantAgreement/ES/ISCIII/JR22-00057
Financiación: info:eu-repo/grantAgreement/ES/ISCIII/RD21-0002-0050
Financiación: info:eu-repo/grantAgreement/ES/ISCIII/RD24-0007-0022
Financiación: info:eu-repo/grantAgreement/ES/MICINN/PID2020-113281RB-C21
Financiación: info:eu-repo/grantAgreement/ES/MICINN/PID2020-113281RB-C22
Tipo y forma: Article (Published version)
Área (Departamento): Área Obstetricia y Ginecología (Dpto. Cirugía)
Área (Departamento): Área Oftalmología (Dpto. Cirugía)
You must give appropriate credit, provide a link to the license, and indicate if changes were made. You may do so in any reasonable manner, but not in any way that suggests the licensor endorses you or your use. You may not use the material for commercial purposes. Exportado de SIDERAL (2025-06-16-09:07:35)
Permalink:
Visitas y descargas
Este artículo se encuentra en las siguientes colecciones:
Articles > Artículos por área > Obstetricia y Ginecología
Articles > Artículos por área > Oftalmología
Record created 2025-06-16, last modified 2025-06-16