Tolerance of high and low amounts of PLGA microspheres loaded with mineralocorticoid receptor antagonist in retinal target site



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Zhao, Min and Rodríguez Villagra, Esther and Kowalczuk, Laura and Le Normand, Manon and Berdugo, Marianne and Levy-Boukris, Rinath and El Zaoui, Ikram and Kaufmann, Béatrice and Gurny, Robert and Bravo-Osuna, Irene and Molina-Martínez, Irene T. and Herrero-Vanrell, Rocío and Behar-Cohen, Francine (2017) Tolerance of high and low amounts of PLGA microspheres loaded with mineralocorticoid receptor antagonist in retinal target site. Journal of Controlled Release, 266 . pp. 187-197. ISSN 0168-3659

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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.

Item Type:Article
Uncontrolled Keywords:Mineralocorticoid receptor, Spironolactone, Microspheres intraocular tolerance, Poly lactic-co-glycolic acid (PLGA), In vivo electroretinography, In vivo optical coherence tomography, Immunohistochemistry
Subjects:Medical sciences > Pharmacy
Medical sciences > Pharmacy > Pharmaceutical technology
ID Code:51766
Deposited On:08 Mar 2019 13:11
Last Modified:11 Mar 2019 08:42

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