title: 28-day intraocular pressure reduction with a single dose of brimonidine tartrate-loaded microspheres.
abstract: Treatment of glaucoma by intraocular pressure (IOP) reduction is typically accomplished through the administration of eye drops, the difficult and frequent nature of which contributes to extremely low adherence rates. Poor adherence to topical treatment regimens in glaucoma patients can lead to irreversible vision loss and increased treatment costs. Currently there are no approved treatments for glaucoma that address the inherent inefficiencies in drug delivery and patient adherence. Brimonidine tartrate (BT), a common glaucoma medication, requires dosing every 8-12 h, with up to 97% of patients not taking it as prescribed. This study provides proof-of-principle testing of a controlled release BT formulation. BT was encapsulated in poly(lactic-co-glycolic) acid microspheres and drug release was quantified using UV-Vis spectroscopy. For in vivo studies, rabbits were randomized to receive a single subconjunctival injection of blank (no drug) or BT-loaded microspheres or twice daily topical 0.2% BT drops. The microspheres released an average of 2.1 ± 0.37 μg BT/mg microspheres/day in vitro. In vivo, the percent decrease in IOP from baseline was significantly greater in the treated eye for both topical drug and drug-loaded microspheres versus blank microspheres throughout the 4-week study, with no evidence of migration or foreign body response. IOP measurements in the contralateral, untreated eyes also suggested a highly localized effect from the experimental treatment. A treatment designed using the release systems described in this study would represent a vast improvement over the current clinical standard of 56-84 topical doses over 28 days.
authors: UPMC Eye Center, Department of Ophthalmology, University of Pittsburgh School of Medicine, 203 Lothrop St., Pittsburgh, PA 15213, USA; The Louis J. Fox Center for Vision Restoration of UPMC and University of Pittsburgh, 3700 O'Hara St., Pittsburgh, PA 15261, USA; Department of Chemical Engineering, Swanson School of Engineering, University of Pittsburgh, 3700 O'Hara St., Pittsburgh, PA 15261, USA; The McGowan Institute for Regenerative Medicine of UPMC and University of Pittsburgh, USA. Electronic address: mod8@pitt.edu.
authors: Morgan V
authors: MV
authors: Fedorchak
authors: UPMC Eye Center, Department of Ophthalmology, University of Pittsburgh School of Medicine, 203 Lothrop St., Pittsburgh, PA 15213, USA. Electronic address: connerip@upmc.edu.
authors: Ian P
authors: IP
authors: Conner
authors: UPMC Eye Center, Department of Ophthalmology, University of Pittsburgh School of Medicine, 203 Lothrop St., Pittsburgh, PA 15213, USA. Electronic address: medina25@hotmail.com.
authors: Carlos A
authors: CA
authors: Medina
authors: UPMC Eye Center, Department of Ophthalmology, University of Pittsburgh School of Medicine, 203 Lothrop St., Pittsburgh, PA 15213, USA. Electronic address: jbwingard@gmail.com.
authors: Jeremy B
authors: JB
authors: Wingard
authors: UPMC Eye Center, Department of Ophthalmology, University of Pittsburgh School of Medicine, 203 Lothrop St., Pittsburgh, PA 15213, USA; The Louis J. Fox Center for Vision Restoration of UPMC and University of Pittsburgh, 3700 O'Hara St., Pittsburgh, PA 15261, USA; Department of Bioengineering, Swanson School of Engineering, University of Pittsburgh, 3700 O'Hara St., Pittsburgh, PA 15261, USA; The McGowan Institute for Regenerative Medicine of UPMC and University of Pittsburgh, USA. Electronic address: schumanjs@upmc.edu.
authors: Joel S
authors: JS
authors: Schuman
authors: UPMC Eye Center, Department of Ophthalmology, University of Pittsburgh School of Medicine, 203 Lothrop St., Pittsburgh, PA 15213, USA; Department of Chemical Engineering, Swanson School of Engineering, University of Pittsburgh, 3700 O'Hara St., Pittsburgh, PA 15261, USA; Department of Bioengineering, Swanson School of Engineering, University of Pittsburgh, 3700 O'Hara St., Pittsburgh, PA 15261, USA; Department of Immunology, University of Pittsburgh, 3700 O'Hara St., Pittsburgh, PA 15261, USA; The McGowan Institute for Regenerative Medicine of UPMC and University of Pittsburgh, USA. Electronic address: srlittle@pitt.edu.
authors: Steven R
authors: SR
authors: Little
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D000068438:Brimonidine Tartrate; D016503:Drug Delivery Systems / Q000379:methods*; D007429:Intraocular Pressure / Q000187:drug effects*; D008863:Microspheres; D023421:Models, Animal; D011810:Quinoxalines / Q000008:administration & dosage / Q000494:pharmacology*; D011817:Rabbits
chemical_list: D000959:Antihypertensive Agents; D011810:Quinoxalines; D000068438:Brimonidine Tartrate
keywords: brimonidine; controlled release; glaucoma; intraocular pressure; microsphere; polymer; rabbit