Multi-loaded PLGA microspheres as neuroretinal therapy in a chronic glaucoma animal model

Aragón-Navas, Alba ; Rodrigo, Maria Jesus (Universidad de Zaragoza) ; Munuera, Inés (Universidad de Zaragoza) ; García-Herranz, David ; Subías, Manuel (Universidad de Zaragoza) ; Villacampa, Pilar ; García-Feijoo, Julián ; Pablo, Luis (Universidad de Zaragoza) ; Garcia-Martin, Elena (Universidad de Zaragoza) ; Herrero-Vanrell, Rocio ; Bravo-Osuna, Irene

Resumen: This work focused on the co-encapsulation and simultaneous co-delivery of three different neuroprotective drugs in PLGA (poly(lactic-co-glycolic acid) microspheres for the treatment of glaucoma. For formulation optimization, dexamethasone (anti-inflammatory) and ursodeoxycholic acid (anti-apoptotic) were co-loaded by the solid-in-oil-in-water emulsion solvent extraction-evaporation technique as a first step. The incorporation of a water-soluble co-solvent (ethanol) and different amounts of dexamethasone resulted critical for the encapsulation of the neuroprotective agents and their initial release. The optimized formulation was obtained with 60 mg of dexamethasone and using an 80:20 dichloromethane:ethanol ratio. In the second step in the microencapsulation process, the incorporation of the glial cell line-derived neurotrophic factor (GDNF) was performed. The final prototype showed encapsulation efficiencies for each component above 50% with suitable properties for long-term application for at least 3 months. Physicochemical studies were performed by SEM, TEM, DSC, XRD, and gas chromatography. The evaluation of the kinetic release by the Gallagher-Corrigan analysis with Gorrasi correction helped to understand the influence of the co-microencapsulation on the delivery of the different actives from the optimized formulation. The final prototype was tested in a chronic glaucoma animal model. Rats received two intravitreal injections of the neuroprotective treatment within a 24-week follow-up study. The proposed formulation improved retinal ganglion cell (RGC) functionality examined by electroretinography. Also, it was able to maintain a neuroretinal thickness similar to that of healthy animals scanned by in vivo optical coherence tomography, and a higher RGC count on histology compared to glaucomatous animals at the end of the study.

Idioma: Inglés

DOI: 10.1007/s13346-024-01702-x

Año: 2024

Publicado en: Drug Delivery and Translational Research (2024), [25 pp.]
ISSN: 2190-393X

Financiación: info:eu-repo/grantAgreement/ES/ISCIII-FEDER-RETICS/RD16-0008-0004
Financiación: info:eu-repo/grantAgreement/ES/ISCIII-FEDER-RETICS/RD16-0008-0009
Financiación: info:eu-repo/grantAgreement/ES/ISCIII-FEDER-RETICS/RD16-0008-029
Financiación: info:eu-repo/grantAgreement/ES/ISCIII/JR22-00057
Financiación: info:eu-repo/grantAgreement/ES/MICINN/MAT2017-83858-C2-1
Financiación: info:eu-repo/grantAgreement/ES/MICINN/MAT2017-83858-C2-2
Financiación: info:eu-repo/grantAgreement/ES/MICINN/PID2020-113281RB-C21
Financiación: info:eu-repo/grantAgreement/ES/MICINN/PID2020-113281RB-C22
Financiación: info:eu-repo/grantAgreement/ES/MICINN/PRE2018-083951

Tipo y forma: Artículo (Versión definitiva)

Área (Departamento): Área Oftalmología (Dpto. Cirugía)