UC San Diego

ABSTRACT OF THE DISSERTATIONIntravitreal Therapeutic Nanoparticles for the Treatment of Posterior Segment Ocular Diseases Joel F. Grondek Doctor of Philosophy University of California, San Diego, 2021 Professor Michael J. Sailor, Chair Ocular therapeutic delivery affords challenges as unique as the diseases themselves. The human eye is anatomically compartmentalized, both within the organ itself and from the systemic vasculature typically used for drug delivery. Recent pharmaceutical developments have revolutionized the prognosis for ocular diseases, yet many therapies treating the posterior segment of the eye remain invasive and require frequent administration to maintain remission. Herein, we review the application of nanocarriers as intravitreally injected therapeutic delivery vehicles working toward enhanced retinal uptake to further improve current therapeutic outcomes and for the development future therapies and we present a novel approach to the treatment of diabetic retinopathy and diabetic macular edema. Chapter one provides introductory overview of the complex anatomy of the eye, routes of therapeutic administration, and current nanoparticle formulations designed to treat posterior segment diseases by intravitreal injection. Chapter two demonstrates a novel application of fusogenic porous silicon nanoparticles for intravitreal delivery of vascular endothelial growth factor siRNA using a rabbit model for diabetic retinopathy and diabetic macular edema. Chapter three summaries prior work focused on peptide targeted magnetic resonance imaging of myocardial infarction using a fibrin homing peptide. Here we demonstrate long circulating iron oxide nanoparticle chains call “nanoworms” can effectively target early fibrin associated with myocardial injury using a rat ischemia/reperfusion model.