Ocular drug delivery targeted by iontophoresis in the suprachoroidal space using a microneedle

• Type of Material: Article
• Authors: Jae Hwan Jung, Georgia Institute of Technology; Bryce Chiang, Georgia Institute of Technology; Hans Grossniklaus, Emory University; Mark R. Prausnitz, Emory University
• Language: English
• Date: 2018-05-10
• Publisher: Elsevier: 12 months
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2018 Elsevier B.V.All rights reserved.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.jconrel.2018.03.001
• Title of Journal or Parent Work: Journal of Controlled Release
• ISSN: 0168-3659
• Volume: 277
• Start Page: 14
• End Page: 22
• Grant/Funding Information: This work was supported by the National Institutes of Health [R01 EY022097].
• Keywords: Chemistry, Multidisciplinary; TRANSSCLERAL IONTOPHORESIS; Chemistry; POSTERIOR SEGMENT; Targeted drug delivery; HYDROGEL; COULOMB-CONTROLLED IONTOPHORESIS; Science & Technology; INTRAVITREAL INJECTION; IN-VIVO; Iontophoresis; MODEL; TRIAMCINOLONE ACETONIDE; RABBIT EYE; Suprachoroidal injection; Physical Sciences; Life Sciences & Biomedicine; Pharmacology & Pharmacy; Microneedle; Ocular drug delivery; NANOPARTICLES; Posterior segment
• Research Categories: Health Sciences, Opthamology; Engineering, Biomedical; Health Sciences, Pharmacology

Abstract

Treatment of many posterior-segment ocular indications would benefit from improved targeting of drug delivery to the back of the eye. Here, we propose the use of iontophoresis to direct delivery of negatively charged nanoparticles through the suprachoroidal space (SCS) toward the posterior pole of the eye. Injection of nanoparticles into the SCS of the rabbit eye ex vivo without iontophoresis led to a nanoparticle distribution mostly localized at the site of injection near the limbus and <15% of nanoparticles delivered to the most posterior region of SCS (>9 mm from the limbus). Iontophoresis using a novel microneedle-based device increased posterior targeting with >30% of nanoparticles in the most posterior region of SCS. Posterior targeting increased with increasing iontophoresis current and increasing application time up to 3 min, but further increasing to 5 min was not better, probably due to the observed collapse of the SCS within 5 min after injection ex vivo. Reversing the direction of iontophoretic flow inhibited posterior targeting, with just ~5% of nanoparticles reaching the most posterior region of SCS. In the rabbit eye in vivo, iontophoresis at 0.14 mA for 3 min after injection of a 100 μL suspension of nanoparticles resulted in ~30% of nanoparticles delivered to the most posterior region of the SCS, which was consistent with ex vivo findings. The procedure was well tolerated, with only mild, transient tissue effects at the site of injection. We conclude that iontophoresis in the SCS using a microneedle has promise as a method to target ocular drug delivery within the eye, especially toward the posterior pole.