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: Artículo (Versión definitiva)

Área (Departamento): Área Obstetricia y Ginecología (Dpto. Cirugía)
Área (Departamento): Área Oftalmología (Dpto. Cirugía)