Targeted Delivery of Antiglaucoma Drugs to the Supraciliary Space Using Microneedles

• Type of Material: Article
• Authors: Yoo C. Kim, Georgia Institute of Technology; Henry Edelhauser, Emory University; Mark Prausnitz, Emory University
• Language: English
• Date: 2014-11-01
• Publisher: Association for Research in Vision and Ophthalmology, Inc
• Publication Version: Final Published Version
• Copyright Statement: Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.
• Final Published Version (URL): http://dx.doi.org/10.1167/iovs.14-14651
• Title of Journal or Parent Work: Investigative Ophthalmology and Visual Science
• Volume: 55
• Issue: 11
• Start Page: 7387
• End Page: 7397
• Grant/Funding Information: Supported by NEI EY017045 (YCK, HFE, MRP) and NEI EY022097 (YCK, MRP).
• Keywords: SUPRACHOROIDAL SPACE; SULPROSTONE; glaucoma; OCULAR PHARMACOKINETICS; suprachoroidal; microneedle; Science & Technology; LATANOPROST; INTRAVITREAL; GLAUCOMA; INTRAOCULAR-PRESSURE; POSTERIOR SEGMENT; BRIMONIDINE; Life Sciences & Biomedicine; drug delivery; Ophthalmology; AQUEOUS-HUMOR DYNAMICS
• Research Categories: Health Sciences, Opthamology

Abstract

PURPOSE: In this work, we tested the hypothesis that highly targeted delivery of antiglaucoma drugs to the supraciliary space by using a hollow microneedle allows dramatic dose sparing of the drug compared to topical eye drops. The supraciliary space is the most anterior portion of the suprachoroidal space, located below the sclera and above the choroid and ciliary body. METHODS: A single, hollow 33-gauge microneedle, 700 to 800 μm in length, was inserted into the sclera and used to infuse antiglaucoma drugs into the supraciliary space of New Zealand white rabbits (N = 3-6 per group). Sulprostone, a prostaglandin analog, and brimonidine, an α₂-adrenergic agonist, were delivered via supraciliary and topical administration at various doses. The drugs were delivered unilaterally, and intraocular pressure (IOP) of both eyes was measured by rebound tonometry for 9 hours after injection to assess the pharmacodynamic responses. To assess safety of the supraciliary injection, IOP change immediately after intravitreal and supraciliary injection were compared. RESULTS: Supraciliary delivery of both sulprostone and brimonidine reduced IOP by as much as 3 mm Hg bilaterally in a dose-related response; comparison with topical administration at the conventional human dose showed approximately 100-fold dose sparing by supraciliary injection for both drugs. A safety study showed that the kinetics of IOP elevation immediately after supraciliary and intravitreal injection of placebo formulations were similar. CONCLUSIONS: This study introduced the use of targeted drug delivery to the supraciliary space by using a microneedle and demonstrated dramatic dose sparing of antiglaucoma therapeutic agents compared to topical eye drops. Targeted delivery in this way can increase safety by reducing side effects and could allow a single injection to contain enough drug for long-term sustained delivery.