Controlled delivery of tauroursodeoxycholic acid from biodegradable microspheres slows retinal degeneration and vision loss in P23H rats

Fernandez-Sanchez, L. ; Bravo-Osuna, I. ; Lax, P. ; Arranz-Romera, A. ; Maneu, V. ; Esteban-Perez, S. ; Pinilla, I. (Universidad de Zaragoza) ; Puebla-Gonzalez, M.D. ; Herrero-Vanrell, R. ; Cuenca, N.

Resumen: Successful drug therapies for treating ocular diseases require effective concentrations of neuroprotective compounds maintained over time at the site of action. The purpose of this work was to assess the efficacy of intravitreal controlled delivery of tauroursodeoxycholic acid (TUDCA) encapsulated in poly(D, L-lactic-co-glycolic acid) (PLGA) microspheres for the treatment of the retina in a rat model of retinitis pigmentosa. PLGA microspheres (MSs) containing TUDCA were produced by the O/W emulsion-solvent evaporation technique. Particle size and morphology were assessed by light scattering and scanning electronic microscopy, respectively. Homozygous P23H line 3 rats received a treatment of intravitreal injections of TUDCA-PLGA MSs. Retinal function was assessed by electroretinography at P30, P60, P90 and P120. The density, structure and synaptic contacts of retinal neurons were analyzed using immunofluorescence and confocal microscopy at P90 and P120. TUDCA-loaded PLGA MSs were spherical, with a smooth surface. The production yield was 78%, the MSs mean particle size was 23 mu m and the drug loading resulted 12.5 +/- 0.8 mu g TUDCA/mg MSs. MSs were able to deliver the loaded active compound in a gradual and progressive manner over the 28-day in vitro release study. Scotopic electroretinografic responses showed increased ERG a- and b-wave amplitudes in TUDCA-PLGA-MSstreated eyes as compared to those injected with unloaded PLGA particles.TUDCA-PLGAMSs- treated eyes showed more photoreceptor rows than controls. The synaptic contacts of photoreceptors with bipolar and horizontal cells were also preserved in P23H rats treated with TUDCA-PLGA MSs. This work indicates that the slow and continuous delivery of TUDCA from PLGA-MSs has potential neuroprotective effects that could constitute a suitable therapy to prevent neurodegeneration and visual loss in retinitis pigmentosa.

Idioma: Inglés

DOI: 10.1371/journal.pone.0177998

Año: 2017

Publicado en: PloS one 12, 5 (2017), e0177998[20 pp]
ISSN: 1932-6203

Factor impacto JCR: 2.766 (2017)

Categ. JCR: MULTIDISCIPLINARY SCIENCES rank: 15 / 64 = 0.234 (2017) - Q1 - T1

Factor impacto SCIMAGO: 1.164 - Agricultural and Biological Sciences (miscellaneous) (Q1) - Medicine (miscellaneous) (Q1) - Biochemistry, Genetics and Molecular Biology (miscellaneous) (Q1)

Financiación: info:eu-repo/grantAgreement/ES/ISCIII/RETICS-FEDER-RD16-0008-0009
Financiación: info:eu-repo/grantAgreement/ES/ISCIII/RETICS-FEDER-RD16-0008-0016
Financiación: info:eu-repo/grantAgreement/ES/MICINN-FEDER/MAT2013-43127R
Financiación: info:eu-repo/grantAgreement/ES/MINECO-FEDER/BFU2015-67139-R

Tipo y forma: Artículo (Versión definitiva)

Área (Departamento): Área Oftalmología (Dpto. Cirugía,Ginecol.Obstetr.)