Targeted Administration into the Suprachoroidal Space Using a Microneedle for Drug Delivery to the Posterior Segment of the Eye

• Type of Material: Article
• Authors: Samirkumar R. Patel, Georgia Institute of Technology; Damian Berezovsky, Emory University; Bernard E. McCarey, Emory University; Vladimir Zarnitsyn, Georgia Institute of Technology; Henry Edelhauser, Emory University; Mark Prausnitz, Emory University
• Language: English
• Date: 2012-07-01
• Publisher: Association for Research in Vision and Ophthalmology (ARVO)
• Publication Version: Final Published Version
• Copyright Statement: © 2012 The Association for Research in Vision and Ophthalmology, Inc.
• Final Published Version (URL): http://dx.doi.org/10.1167/iovs.12-9872
• Title of Journal or Parent Work: Investigative Ophthalmology & Visual Science
• ISSN: 0146-0404
• Volume: 53
• Issue: 8
• Start Page: 4433
• End Page: 4441
• Grant/Funding Information: Supported by National Eye Institute Grant R24-EY-017045 and an unrestricted grant from Research to Prevent Blindness.
• Keywords: Ophthalmology; Science & Technology; Life Sciences & Biomedicine; INTRAVITREAL INJECTION; MACULAR DEGENERATION
• Research Categories: Engineering, Biomedical; Health Sciences, Medicine and Surgery

Abstract

Purpose: This study seeks to determine the intraocular pharmacokinetics of molecules and particles injected into the suprachoroidal space of the rabbit eye in vivo using a hollow microneedle. Methods. Suprachoroidal injections of fluorescein and fluorescently tagged dextrans (40 and 250 kDa), bevacizumab, and polymeric particles (20 nm to 10 μm in diameter) were performed using microneedles in New Zealand white rabbits. The fluorescence intensity within the eye was monitored in each animal using an ocular fluorophotometer to determine the distribution of the injected material in the eye over time as compared with intravitreal injection of fluorescein. Fundus photography and histology were performed as well. Results. Molecules and particles injected near the limbus using a microneedle flowed circumferentially around the eye within the suprachoroidal space. By targeting the suprachoroidal space, the concentration of injected materials was at least 10-fold higher in the back of the eye tissues than in anterior tissues. In contrast, intravitreal injection of fluorescein targeted the vitreous humor with no significant selectivity for posterior versus anterior segment tissues. Half-lives in the suprachoroidal space for molecules of molecular weight from 0.3 to 250 kDa ranged from 1.2 to 7.9 hours. In contrast, particles ranging in size from 20 nm to 10 μm remained primarily in the suprachoroidal space and choroid for a period of months and did not clear the eye. No adverse effects of injection into the suprachoroidal space were observed. Conclusion. Injection into the suprachoroidal space using a microneedle offers a simple and minimally invasive way to target the delivery of drugs to the choroid and retina.