Thickness and closure kinetics of the suprachoroidal space following microneedle injection of liquid formulations

• Authors: Bryce Chiang, Georgia Institute of Technology; Nitin Venugopal, Georgia Institute of Technology; Hans Grossniklaus, Emory University; Jae Hwan Jung, Georgia Institute of Technology; Henry Edelhauser, Emory University; Mark Prausnitz, Emory University
• Journal Title: Investigative Ophthalmology & Visual Science
• Volume: Volume 58, Number 1
• Publisher: Association for Research in Vision and Ophthalmology (ARVO) | 2017-01-01, Pages 555-564
• Type of Work: Article | Final Publisher PDF
• Publisher DOI: http://doi.org/10.1167/iovs.16-20377
• Subjects: Engineering, Biomedical; Biology, Molecular; Engineering, Industrial
• Keywords: suprachoroidal space; suprachoroidal space thickness; microneedle injection; ocular drug deliver; 3D cryo-reconstruction

Abstract

Purpose To determine the effect of injection volume and formulation of a microneedle injection into the suprachoroidal space (SCS) on SCS thickness and closure kinetics. Methods Microneedle injections containing 25 to 150 μL Hanks' balanced salt solution (HBSS) were performed in the rabbit SCS ex vivo. Distribution of SCS thickness was measured by ultrasonography and three-dimensional (3D) cryo-reconstruction. Microneedle injections were performed in the rabbit SCS in vivo using HBSS, Discovisc, and 1% to 5% carboxymethyl cellulose (CMC) in HBSS. Ultrasonography was used to track SCS thickness over time. Results Increasing HBSS injection volume increased the area of expanded SCS, but did not increase SCS thickness ex vivo. With SCS injections in vivo, the SCS initially expanded to thicknesses of 0.43 ± 0.06 mm with HBSS, 1.5 ± 0.4 mm with Discovisc, and 0.69 to 2.1 mm with 1% to 5% CMC. After injection with HBSS, Discovisc, and 1% CMC solution, the SCS collapsed to baseline with time constants of 19 minutes, 6 hours, and 2.4 days, respectively. In contrast, injections with 3% to 5% CMC solution resulted in SCS expansion to 2.3 to 2.8 mm over the course of 2.8 to 9.1 hours, after which the SCS collapsed to baseline with time constants of 4.5 to 9.2 days. Conclusions With low-viscosity formulations, SCS expands to a thickness that remains roughly constant, independent of the volume of fluid injected. Increasing injection fluid viscosity significantly increased SCS thickness. Expansion of the SCS is hypothesized to be controlled by a balance between the viscous forces of the liquid formulation and the resistive biomechanical forces of the tissue.