Evaluation of Nano-Formulated Neuroprotective Against Traumatic Brain Injury

Repetitive traumatic brain injuries (TBI) can lead to progressive degeneration of brain tissue, resulting in chronic traumatic encephalopathy. Generation of oxidative stress (reactive oxygen species (ROS)), neuro-inflammation and mitochondrial dysfunction have all been implicated in the process of neurodegeneration associated with TBI. The loss of structure and function of neurons results in symptoms similar to neurodegenerative diseases such as Parkinson’s, Huntington’s and Alzheimer’s. In this work we investigate the ability of nanoparticles to enhance the delivery of antioxidants to neuronal cells and protect against oxidative stress and impaired behavior from TBI.

Polyanhydride nanoparticles can be designed to elicit unique cellular responses by stimulating particle internalization and directing intracellular trafficking. By encapsulating the payload within the polyanhydride particles sustained release of these compounds over time can be achieved. Through modifications in the polymer chemistry, surface functionalization and particle size, the release kinetics of payloads and the fate of the particle within target cells can be tailored. In this work, the neuroprotective payload of interest is an anti-oxidant, mito-apocynin, which has been tailored to target mitochondria. The biodistribution of the mito-apocynin is evaluated through quantification of the compound in both target (i.e., brain) and off target tissues. Efficacy of the nano-formulated treatment is evaluated through a combination of cognitive function (i.e., locomotor activity) and neuronal loss.