Date of Award
Master of Science
Chemical and Biological Engineering
Surya K. Mallapragada
Neurodegenerative diseases are a large burden to the society. They are characterized by a loss of neuronal cells that affect the ability to perform daily activities, and are often caused by environmental or genetic factors. Therapeutics can treat clinical symptoms of chronic disease, but there is a need to additionally treat the underlying mechanisms leading to neuronal atrophy, such as mitochondrial dysfunction and inflammation. Efficacious treatment is very difficult due to the existence of several physiological hurdles, including the blood-brain barrier, diseased neuron, and intracellular organelle. Targeted nano-carriers can enhance local bioavailability by targeting each of these hurdles. Polyanhydride nanoparticles (NPs) in particular are attractive nano-carriers for central nervous system delivery of therapeutics, and can easily be functionalized with targeting ligands to further improve delivery.
The goal of the project detailed herein is to rationally design a functionalized polyanhydride NP drug delivery platform addressing all physiological hurdles of the neurovascular unit to combat neurodegeneration. First, functionalized and non-functionalized 20:80 CPH:SA polyanhydride NPs were evaluated for the ability to cross the BBB in vitro. These NPs demonstrated promise in the ability to cross the BBB. Second, bulk-functionalized 20:80 CPH:SA NPs were evaluated for the ability to be internalized by neurons and enhance protective capability of antioxidants against oxidative stress in vitro. It was found that the functionalized NPs demonstrated superior internalization by N27 neurons compared to non-functionalized NPs, and antioxidant-loaded NPs protected against hydrogen peroxide – induced oxidative stress. Collectively, these studies lay the foundation for further investigation of the functionalized NP platform for central nervous system drug delivery.
Benjamin William Schlichtmann
Schlichtmann, Benjamin William, "Targeted nano-carriers to combat neurodegeneration" (2017). Graduate Theses and Dissertations. 16294.