title: Sustained reduction of intraocular pressure by supraciliary delivery of brimonidine-loaded poly(lactic acid) microspheres for the treatment of glaucoma.
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 poly(lactic 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 mmHg 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.
authors.affiliation: Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta GA 30332, USA.
authors.forename: B
authors.initials: B
authors.lastname: Chiang
authors.affiliation: School of Chemical & Biomolecular Engineering, Georgia Institute of Technology, Atlanta GA 30332, USA.
authors.forename: Y C
authors.initials: YC
authors.lastname: Kim
authors.affiliation: Department of Pharmaceutical Sciences, The Biointerfaces Institute, University of Michigan, North Campus Research Complex, 2800 Plymouth Road, Ann Arbor MI 48109, USA.
authors.forename: A C
authors.initials: AC
authors.lastname: Doty
authors.affiliation: Department of Ophthalmology, Emory University School of Medicine, Atlanta GA 30322, USA.
authors.forename: H E
authors.initials: HE
authors.lastname: Grossniklaus
authors.affiliation: Department of Pharmaceutical Sciences, The Biointerfaces Institute, University of Michigan, North Campus Research Complex, 2800 Plymouth Road, Ann Arbor MI 48109, USA.
authors.forename: S P
authors.initials: SP
authors.lastname: Schwendeman
authors.affiliation: Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta GA 30332, USA; School of Chemical & Biomolecular Engineering, Georgia Institute of Technology, Atlanta GA 30332, USA. Electronic address: prausnitz@gatech.edu.
authors.forename: M R
authors.initials: MR
authors.lastname: Prausnitz
mesh_terms: D000818:Animals; D000869:Anterior Eye Segment / Q000187:drug effects / Q000378:metabolism; D000959:Antihypertensive Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D000068438:Brimonidine Tartrate / Q000008:administration & dosage* / Q000627:therapeutic use; D003692:Delayed-Action Preparations / Q000737:chemistry*; D016503:Drug Delivery Systems / Q000295:instrumentation; D005901:Glaucoma / Q000188:drug therapy* / Q000378:metabolism; D007267:Injections; D007429:Intraocular Pressure / Q000187:drug effects*; D008863:Microspheres; D009339:Needles; D011091:Polyesters / Q000737:chemistry*; D011817:Rabbits
chemical_list: D000959:Antihypertensive Agents; D003692:Delayed-Action Preparations; D011091:Polyesters; C033616:poly(lactide); D000068438:Brimonidine Tartrate
keywords: Brimonidine; Glaucoma; Microneedles; New Zealand White rabbit; Suprachoroidal space