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Author Notes:

Mark R. Prausnitz, School of Chemical and Biomolecular Engineering, Georgia Institute of Technology, 311 Ferst Drive, Atlanta, GA 30332, USA; Email: prausnitz@gatech.edu

The authors thank Henry Edelhauser, Timothy Olsen, and Pradnya Samant for helpful discussions; Jae Hwan Jung and Brandon Gerberich for assistance with experiments; Machelle Pardue for use of the RetCam; and Donna Bondy for administrative support.

This work was carried out at the Institute for Bioengineering and Bioscience and Center for Drug Design, Development and Delivery at Georgia Tech.

Disclosure: B. Chiang, P; K. Wang, None; C.R. Ethier, None; M.R. Prausnitz, Clearside Biomedical (I, S), P

Subjects:

Research Funding:

Supported by National Eye Institute grants EY017045 (BC, MRP), EY022097 (BC, MRP), EY007092 (BC), and EY025154 (BC).

Keywords:

  • ophthalmic drug delivery kinetics
  • suprachoroidal space of eye
  • microneedle injection
  • transscelral clearance
  • perivascular drainage
  • injection site reflux
  • random walk model

Clearance Kinetics and Clearance Routes of Molecules From the Suprachoroidal Space After Microneedle Injection.

Tools:

Journal Title:

Investigative Ophthalmology & Visual Science

Volume:

Volume 58, Number 1

Publisher:

, Pages 545-554

Type of Work:

Article | Final Publisher PDF

Abstract:

Purpose: To determine clearance kinetics and routes of clearance of molecules from the suprachoroidal space (SCS) of live New Zealand White rabbits. Methods: Suprachoroidal space collapse rate and pressure changes after microneedle injection into SCS were determined. Fluorescent fundus images were acquired to determine clearance rates of molecules ranging in size from 332 Da to 2 MDa. Microneedle injections of fluorescein were performed, and samples were taken from various sites over time to determine amount of fluorescein exiting the eye. Clearance transport was modeled theoretically and compared with experimental data. Results: After injection, pressures in SCS and vitreous humor spiked and returned to baseline within 20 minutes; there was no difference between these two pressures. Suprachoroidal space collapse occurred within 40 minutes. One hour after fluorescein injection, 46% of fluorescein was still present in the eye, 15% had transported across sclera, 6% had been cleared by choroidal vasculature, and 4% had exited via leakage pathways. Characteristic clearance time increased in proportion with molecular radius, but total clearance of 2 MDa FITC-dextran was significantly slower (21 days) than smaller molecules. These data generally agreed with predictions from a theoretical model of molecular transport. Conclusions: Guided by experimental data in the context of model predictions, molecular clearance from SCS occurred in three regimes: (1) on a time scale of approximately 10 minutes, fluid and molecules exited SCS by diffusion into sclera and choroid, and by pressure-driven reflux via transscleral leakage sites; (2) in approximately 1 hour, molecules cleared from choroid by blood flow; and (3) in 1 to 10 hours, molecules cleared from sclera by diffusion and convection.

Copyright information:

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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