Nanoparticle-Mediated Drug Delivery for Neurodegenerative Brain Diseases
Date
2020-05
Authors
Harris, Ashley
Major Professor
Advisor
Narasimhan, Balaji
Committee Member
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Abstract
Neurodegenerative diseases, such as Parkinson’s Disease (PD), affect millions of Americans every year. Currently approved PD therapeutics treat motor symptoms, but do not slow down disease progression. Additionally, high therapeutic doses are needed due to complications crossing the Blood-brain Barrier (BBB), leading to unwanted side effects. Nanoparticles (NPs) can address these challenges by improving brain bioavailability of disease-slowing anti-neurodegenerative therapeutics. Specifically, polyanhydride NPs can improve therapeutic efficacy by crossing the BBB and releasing the drug at the right time, and can be functionalized to further improve brain bioavailability. In this study, to investigate this platform, polyanhydride NP-drug interaction properties of therapeutic-encapsulated functionalized and non-functionalized NPs are evaluated. A correlation with drug hydrophobicity was found regardless of functionalization, where sustained release was observed for hydrophobic drugs, while hydrophilic drugs experienced a large “burst” release within the first day with trace amounts released thereafter. The difference in encapsulation efficiency (EE) between hydrophilic and hydrophobic drugs was not significant. Additionally, surfactants were considered in an effort to provide sustained release and raise the EE. However, incorporating span-80 during NP synthesis did not lead to improved sustained release or EE. Future studies will investigate cellular internalization efficiency in neurons, microglia, astrocytes and endothelial cells.
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