RT Journal Article
T1 Tolerance of high and low amounts of PLGA microspheres loaded with mineralocorticoid receptor antagonist in retinal target site
A1 Zhao, Min
A1 Rodríguez Villagra, Esther
A1 Kowalczuk, Laura
A1 Le Normand, Manon
A1 Berdugo, Marianne
A1 Levy-Boukris, Rinath
A1 El Zaoui, Ikram
A1 Kaufmann, Béatrice
A1 Gurny, Robert
A1 Bravo Osuna, Irene
A1 Molina Martínez, Irene Teresa
A1 Herrero Vanrell, María Del Rocío
A1 Behar-Cohen, Francine
AB Mineralocorticoid receptor (MR)contributes to retinal/choroidal homeostasis. Excess MR activation has been shown to be involved in pathogenesis of central serous chorioretinopathy (CSCR). Systemic administration of MR antagonist (MRA) reduces subretinal fluid and choroidal vasodilation, and improves the visual acuity in CSCR patients. To achieve long term beneficial effects in the eye while avoiding systemic side-effects, we propose the use ofbiodegradable spironolactone-loaded polylactic-co-glycolic acid (PLGA)microspheres (MSs). In this work we have evaluated the ocular tolerance of MSs containing spironolactone in rats’ eyes. As previous step, we have also studied the tolerance of the commercial solution of canrenoate salt, active metabolite of spironolactone. PLGA MSs allowed in vitro sustained release of spironolactone for 30 days. Rat eyes injected with high intravitreous concentration of PLGA MSs (10 mg/mL) unloaded and loaded with spironolactone maintained intact retinal lamination at 1 month. However enhanced glial fibrillary acidic protein immunostaining and activated microglia/macrophages witness retinal stress were observed. ERG also showed impaired photoreceptor function. Intravitreous PLGA MSs concentration of 2 mg/mL unloaded and loaded with spironolactone resulted well tolerated. We observed reduced microglial/macrophage activation in rat retina compared to high concentration of MSs with normal retinal function according to ERG. Spironolactone released from low concentration of MSs was active in the rat retina. Low concentration of spironolactone-loaded PLGA MSs could be a safe therapeutic choice for chorioretinal disorders in which illicit MR activation could be pathogenic.
PB Elsevier
SN 0168-3659
YR 2017
FD 2017-11-28
LK https://hdl.handle.net/20.500.14352/18741
UL https://hdl.handle.net/20.500.14352/18741
LA eng
NO Ministerio de Economía, Comercio y Empresa (España)/Fondo Europeo de Desarrollo Regional
NO Instituto de Salud Carlos III
NO Universidad Complutense de Madrid
NO Agence Nationale de la Recherche (Francia)
NO Fondation de la Recherche Médicale (Francia)
DS Docta Complutense
RD 9 abr 2025