Cell Biology and Genetics Classification: GSBS Student1, Vishwanatha, Jamboor K. 2 1 Dept. of Cell Biology and Genetics, 2 Dept. of Molecular Biology and Immunology, University of North Texas Health Science Center, Fort Worth, TX, 76107
FORMULATION AND CHARACTERIZATION OF NACETYL CYSTEINE LOADED PLGA NANOPARTICLES FOR NEUROPROTECTION TO RETINAL GANGLION CELLS IN AN IN VITRO MODEL OF GLAUCOMATOUS CELL DEATH
Purpose: from peripheral circulation via the blood retina barrier. Likewise, polyLlacticco
glycolic acid (PLGA) is a preferential polymer to encapsulate drugs for sustained delivery because it isbiodegradable, biocompatible and FDA approved. The purpose of this study is to formulate andcharacterize Nacetyl cysteine (NAC) loaded PLGA nanoparticles and study the effect of themdelivering neuroprotective antioxidants to retinal ganglion cells. We hypothesize that NAC loaded PLGA nanoparticles (NACPLGAnps) will afford sustained neuroprotection to retinal ganglion cells (RGCs) via activation of cell survival pathways when compared to NAC alone.
The eye is a preferential environment to study sustained delivery methods due to its isolation
Methods: technique. Nanoparticles were then characterized for size using a particle size analyzer, Nanotrac. Intracellular localization in RGC5 and to the RGC cell layer in pig eyes was determined using Nile Red. Encapsulation efficiency was determined by direct method utilizing the thiolreactive probe, Ellmans Reagent. Western blotting analysis was used for determination of cell signaling events.
PLGA nanoparticles were synthesized utilizing double emulsion solvent evaporation
nps were optimized based on preferred size (100250 nm) and encapsulation efficiency. It was found that NACPLGA nps localize intracellularly in vitro in RGC5s and ex vivo to RGCs in pig eyes. NACPLGA nps induce sustained phosphorylation of ERK1 and 2, and S6 over 24 hours compared with control.
Conclusions: nanoparticles have potential to become an effective treatment, in vitro, against the generation of oxidative stress and cytotoxicity. They are a plausible for application in glaucoma because of the ability to localize intracellularly in RGCs. The application of such a sustained delivery method could improve patient outcomes and compliance when combined with IOPlowering treatments or in normal tension glaucomas alone.