Suprachoroidal Delivery in Rats and Guinea Pigs Using a High-Precision Microneedle Injector

• Type of Material: Article
• Authors: Amir Hejri, Georgia Institute of Technology, Atlanta; Issabella I Bowland, Georgia Institute of Technology, Atlanta; John Nickerson, Emory University; Mark Prausnitz, Emory University
• Language: English
• Date: 2023-03-01
• Publisher: ASSOC RESEARCH VISION OPHTHALMOLOGY INC
• Publication Version: Final Published Version
• Copyright Statement: 2023 The Authors
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1167/tvst.12.3.31
• Title of Journal or Parent Work: TRANSLATIONAL VISION SCIENCE & TECHNOLOGY
• Volume: 12
• Issue: 3
• Start Page: 31
• End Page: 31
• Grant/Funding Information: Supported by National Institutes of Health grants (R01EY02209, R01EY028450, R01EY021592, P30EY006360, and T32EY07092).
• Keywords: THICKNESS; TRIAMCINOLONE ACETONIDE; SPACE; Ophthalmology; suprachoroidal space injection; Science & Technology; posterior segment; ocular drug delivery; DRUG-DELIVERY; MODEL; microneedle injector; GENE DELIVERY; Life Sciences & Biomedicine; SCLERA; rodent eye
• Research Categories: Health Sciences, Opthamology

Abstract

Purpose: Methods of injection into the suprachoroidal space (SCS) have been developed for larger animals and humans, but reliable administration to the SCS of rodents remains challenging given their substantially smaller eyes. Here, we developed microneedle (MN)-based injectors for SCS delivery in rats and guinea pigs. Methods: We optimized key design features, including MN size and tip characteristics, MN hub design, and eye stabilization, to maximize injection reliability. Performance of the injection technique was characterized in rats (n = 13) and guinea pigs (n = 3) in vivo using fundoscopy and histological examinations to validate targeted SCS delivery. Results: To enable SCS injection across the thin rodent sclera, the injector featured an ultrasmall, hollow MN measuring 160 μm in length for rats and 260 μm for guinea pigs. To control MN interaction with the scleral surface, we incorporated a three-dimensional (3D) printed needle hub to restrict scleral deformation at the injection site. A MN tip outer diameter of 110 μm and bevel angle of 55° optimized insertion without leakage. Additionally, a 3D printed probe was used to secure the eye by applying gentle vacuum. Injectionbythistechniquetook1minute to perform,was conducted without an operating microscope, and yielded a 100% success rate (19 of 19) of SCS delivery determined by fundoscopy and histology. A 7-day safety study revealed no notable adverse ocular effects. Conclusions: We conclude that this simple, targeted, and minimally invasive injection technique can enable SCS injection in rats and guinea pigs. Translational Relevance: This MN injector for rats and guinea pigs will expand and expedite preclinical investigations involving SCS delivery.