Initial Safety Results of a Novel Degradable Polymer for Ocular Drug Delivery

Abstract

Purpose: : To test acute ocular safety of a novel degradable polyester-urethane-(meth)acrylate microsphere drug delivery system via a single intravitreal injection toxicity study (28-Day observation period) in New Zealand White Rabbits. The system is designed for treatment of retinal disorders.

Methods: : Whole microspheres (MS) (20-45 µm) and rapidly degraded MS (RDMS) test articles in suspension fluid were injected intravitreally into right eyes of New Zealand White rabbits. Control samples of corresponding right eye suspension fluid were injected into left eyes. Observations included ophthalmoscopy, tonometry and electroretinography. After 28 days rabbits were euthanized and eyes and optic nerves were evaluated by histopathology. The MS samples were prepared by single emulsion water in oil technique from polyester-urethane-(meth)acrylates followed by photopolymerisation. The RDMS samples were prepared by accelerated hydrolytic degradation from the MS samples to mimic various stages of degradation in-vivo.

Results: : Preliminary results were positive in all animals. Only minor opacity in lens, retina and vitreous for some test articles were observed. Intraocular pressure remained within acceptable ranges throughout the study. Uveitis (occurred in one animal), was the only observed ocular adverse event and was believed to be related to the injection procedure. Other results will be presented.

Conclusions: : Conclusions based on pending results will be presented, including histopathology.

Keywords: retina • vitreous • injection