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

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Title: Controlled delivery of tauroursodeoxycholic acid from biodegradable microspheres slows retinal degeneration and vision loss in P23H rats
Authors: Fernández-Sánchez, Laura | Bravo-Osuna, Irene | Lax, Pedro | Arranz-Romera, Alicia | Maneu, Victoria | Esteban-Pérez, Sergio | Pinilla Lozano, Isabel | Puebla-González, María del Mar | Herrero-Vanrell, Rocío | Cuenca, Nicolás
Research Group/s: Neurobiología del Sistema Visual y Terapia de Enfermedades Neurodegenerativas (NEUROVIS)
Center, Department or Service: Universidad de Alicante. Departamento de Fisiología, Genética y Microbiología | Universidad de Alicante. Departamento de Óptica, Farmacología y Anatomía | Universidad de Alicante. Instituto Multidisciplinar para el Estudio del Medio "Ramón Margalef"
Keywords: Retinal degeneration | Vision loss | Tauroursodeoxycholic acid | Biodegradable microspheres | Retinitis pigmentosa
Knowledge Area: Biología Celular | Fisiología | Farmacología
Issue Date: 25-May-2017
Publisher: Public Library of Science (PLoS)
Citation: Fernández-Sánchez L, Bravo-Osuna I, Lax P, Arranz-Romera A, Maneu V, Esteban-Pérez S, et al. (2017) Controlled delivery of tauroursodeoxycholic acid from biodegradable microspheres slows retinal degeneration and vision loss in P23H rats. PLoS ONE 12(5): e0177998.
Abstract: 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 μm and the drug loading resulted 12.5 ± 0.8 μg 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-MSs-treated eyes as compared to those injected with unloaded PLGA particles. TUDCA-PLGA-MSs-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.
Sponsor: This work was supported by The Spanish Ministry of Economy and Competitiveness (MINECO-FEDER BFU2015-67139-R, to NC; MICINN-FEDER MAT 2013–43127R to RH-V) (; Instituto de Salud Carlos III (RETICS-FEDER RD16/0008/0016, to NC; RD16/0008/0009 to RH-V) (; Complutense Research Group (UCM 920415) to RH-V (; and Generalitat Valenciana PROMETEO/2016/158 to NC (
ISSN: 1932-6203
DOI: 10.1371/journal.pone.0177998
Language: eng
Type: info:eu-repo/semantics/article
Rights: © 2017 Fernández-Sánchez et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Peer Review: si
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Appears in Collections:INV - NEUROVIS - Artículos de Revistas

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