Optimized microspheres for sustained delivery: preservation of vision in a model of glaucoma

Abstract

Purpose : The goal of this study is the generation of microspheres that provide sustained delivery of a neuroprotective protein and preserve vision in glaucoma.

Methods : Reactive oxygen species (ROS)-degradable polysulfide microspheres were optimized for increased loading and duration of sustained release of erythropoietin (EPO). Polymer composition was optimized by copolymerization of propylene and ethylene sulfide (PPSES), with ES added to increase polymer crystallinity and structural integrity of resulting microspheres. Glaucoma was induced by intracameral injection of microbeads. At 1-week post-IOP elevation mice were intravitreally injected with loaded or empty microspheres, buffer, or free EPO. EPO content was measured over time. ROS level, photopic negative response (PhNR), visual evoked potential (VEP), and optic nerve structure were assessed at 6 weeks post-treatment.

Results : The resulting PPSES.EPO microspheres exhibited a mean diameter of 58.1±34.6 µm and retained a spherical shape. The increased structural integrity also increased loading and duration of sustained release of purified erythropoietin (EPO). PPSES.EPO had no effect on IOP in this glaucoma model. Treated glaucoma eyes contained 10-22 mU/ml EPO, which was maintained for 6 weeks after a single intravitreal injection. In contrast, eyes treated with empty microspheres contained less than 5 mU/ml endogenous EPO. Glaucoma caused an increase in hydrogen peroxide in the retina. Treatment with empty or EPO-loaded microspheres prevented this increase, although the effect was greatest in the mice treated with PPSES.EPO. The PhNR and VEP were preserved in mice treated with loaded or empty microspheres, but the best protection was in PPSES.EPO treated mice. Total axon counts in treated glaucomatous mice were comparable to non-glaucomatous controls.

Conclusions : The optimized PPSES.EPO microspheres are a promising IOP-independent treatment for glaucoma. PPSES microspheres are themselves antioxidant and therefore are an attractive sustained delivery system for other promising neuroprotective proteins.

This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.