Biocompatibility of Thermo-Responsive Hydrogel Ocular Drug Delivery System in a Rodent Model

Abstract

Purpose: : Recently developed thermo-responsive hydrogel has been shown to be effective in encapsulating and releasing protein and can be utilized as an ocular drug delivery system. The main objective of this study was to investigate the biocompatibility of thermo-responsive hydrogel drug delivery system in a rodent model.

Methods: : All experiments were performed on anesthetized adult pigmented rats. Thermo-responsive hydrogel was synthesized using poly(N-isopropylacrylamide) (PNIPAAm) and crosslinked with polyethylene glycols-diacrylate (PEG-DA). Approximately 3 µl of sterile hydrogel was injected into the vitreous cavity via a 30 gauge needle. Retinal hemodynamics (vasculature, blood velocity and blood flow) were assessed via scanning laser opthalmoscope (SLO) images. Retinal blood velocity was determined by tracking 1 µm yellow-green fluorescent microspheres (505 nm maximum absorption and 515 nm maximum emission). Infrared Reflectance (IR) images were used to measure average vessel diameters. The retinal blood flow of each vessel type was calculated based on cross sectional area and average velocity of the vessel. Data were acquired at prior to injection and weekly up to 4 weeks post injection. Histology was performed after 4 week period.

Results: : There were no significant retinal vasculature structural changes either near the hydrogel or regions away from the hydrogel. The location of the hydrogel remained constant throughout the investigated period. Based on the IR images, there were small vasodilations near the hydrogel by week 3. Near the hydrogel region, there was a small change in the retinal blood flow. No changes in the blood flow were observed in the regions away from the hydrogel. There was no evidence of inflammation.

Conclusions: : There were minimal impacts on the retinal vasculature by the thermo-responsive hydrogel in a rodent model. Current results suggest that thermo-responsive hydrogel may be a safe and promising new non-invasive drug delivery platform to the posterior segment of the eye.

Keywords: retina • blood supply