Sustained reduction of intraocular pressure by supraciliary delivery of brimonidine-loaded polylactic acid microspheres for the treatment of glaucomaReportar como inadecuado

Sustained reduction of intraocular pressure by supraciliary delivery of brimonidine-loaded polylactic acid microspheres for the treatment of glaucoma - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

Journal Title:

Journal of Controlled Release


Volume 228


Elsevier | 2016-04-28, Pages 48-57

Type of Work:

Article | Post-print: After Peer Review

Abstract: Although effective drugs that lower intraocular pressure IOP in the management of glaucoma exist, their efficacy is limited by poor patient adherence to the prescribed eye drop regimen. To replace the need for eye drops, in this study we tested the hypothesis that IOP can be reduced for one month after a single targeted injection using a microneedle for administration of a glaucoma medication i.e., brimonidine formulated for sustained release in the supraciliary space of the eye adjacent to the drug's site of action at the ciliary body. To test this hypothesis, brimonidine-loaded microspheres were formulated using polylactic acid PLA to release brimonidine at a constant rate for 35 days and microneedles were designed to penetrate through the sclera, without penetrating into the choroid-retina, in order to target injection into the supraciliary space. A single administration of these microspheres using a hollow microneedle was performed in the eye of New Zealand White rabbits and was found to reduce IOP initially by 6 mm Hg and then by progressively smaller amounts for more than one month. All administrations were well tolerated without significant adverse events, although histological examination showed a foreign-body reaction to the microspheres. This study demonstrates, for the first time, that the highly-targeted delivery of brimonidine-loaded microspheres into the supraciliary space using a microneedle is able to reduce IOP for one month as an alternative to daily eye drops.

Subjects: Engineering, Biomedical - Health Sciences, Opthamology - Research Funding: This work was supported by the National Eye Institute grants EY007092 BC, EY025154 BC, EY017045 BC, YCK, MRP, EY022097 BC, YCK, MRP, and EY06360 HEG, and an unrestricted departmental grant from the Research to Prevent Blindness HEG.

Keywords: Science and Technology - Physical Sciences - Life Sciences and Biomedicine - Chemistry, Multidisciplinary - Pharmacology and Pharmacy - Chemistry - Suprachoroidal space - Glaucoma - Brimonidine - Microneedles - New Zealand White rabbit - OPEN-ANGLE GLAUCOMA - SUPRACHOROIDAL SPACE - DRUG-DELIVERY - POSTERIOR SEGMENT - TRIAMCINOLONE ACETONIDE - OCULAR HYPERTENSION - OUTFLOW FACILITY - PORCINE MODEL - EYE MODEL - INTRAVITREAL -

Autor: B Chiang, Y.C. Kim, A.C. Doty, Hans Grossniklaus, S.P. Schwendeman, Mark Prausnitz,



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