The Neuroprotective Efficacy of Antioxidants Against In Vitro Models of Oxidative Stress and Their Theoretical Application Via Intravitreal Injection Encapsulated in Nanoparticles

Abstract

The purpose of this study was to explore the possibility of utilizing antioxidants to mitigate oxidative stress induced apoptosis related to neurodegenerative diseases such as glaucoma. Our hypothesis is that in diseases related to an imbalanced redox status, whatever the primary cause may be, the loss of function may be prevented by antioxidants at the level of alleviating oxidative burden and preventing apoptotic signaling events. Application of these antioxidants to the site of injury can be improved using nanoparticle delivery methods. We have done work to characterize a model of mitochondrial associated oxidative stress induced cell death and obtained neuroprotective profiles on a group of antioxidants using this model. We have found that estrogens and phytoestrogens, as well as thiol containing antioxidants, function well as neuroprotectants in our in vitro model. Nanoparticle delivery of these models is a promising intervention and we therefore did work to optimize the characteristics of encapsulating one of these antioxidants, N-acetyl cysteine, in Poly(lactic-coglycolic acid) nanoparticles, which can be localized to the retina. Intravitreal injection of these particles is the preferred delivery route to retinal cells and has not been fully explored. We provide evidence to suggest that the intravitreal injection of nanoparticles is not detrimental to an animal’s vision. Taken together, the results of our experiments suggest that antioxidants remain a promising intervention in diseases related to mitochondrial associated oxidative stress, and that these drugs, when encapsulated in nanoparticles, can be delivered to the retina via intravitreal injection without deleterious side effects.