After the completion and failure of 44 phase III clinical trials, Traumatic Brain Injury (TBI) continues to be a leading cause of disability, morbidity, and mortality amongst military personnel and civilians of all age groups. TBI is characterized by primary and secondary injury processes of which the secondary injury is defined by oxidative stress, increased energy demands, mitochondrial dysfunction, neuroinflammation, and more; characteristics which are also shared with neurodegenerative diseases. Creatine (Cr) is one of the most abundantly used and studied supplements in the fitness industry which, when in the form of Phosphoryl-Creatine (PCr), directly aids in the conversion of ADP to ATP, particularly in metabolically stressed conditions where oxygen is unavailable, and hypothesized to be a JAK2 inhibitor. Similarly, Tannic Acid (TA) is a polyphenol naturally available in teas and nuts that provides neuroprotective effects against TBI through the PGC-1?/Nrf2/HO-1 pathway. However, bioavailability of these compounds in the brain is limited through oral supplementation. Therefore, increasing the local concentration of these compounds in the brain parenchyma may provide therapeutic benefits after cerebral injury. In this study, efficiently loaded, TA-based Creatine nanoparticles (NPs) were synthesized as a potential therapeutic for secondary TBI and related neuroinflammatory conditions. This nanosystem demonstrates surface chemistry augmentation, high loading efficiency, and biodegradation with 24 hours. Purified NPs had an average hydrodynamic diameter of 200 nm, an average surface charge of -44mV, and a polydispersity index (PDI) of 0.171. Purified particles also demonstrate long shelf life and stability over many months, suggesting this inexpensive formulation could be utilized as a cheap therapeutic in underserved, low-income areas.
| Identifer | oai:union.ndltd.org:ucf.edu/oai:stars.library.ucf.edu:etd2020-2604 |
| Date | 01 January 2023 |
| Creators | Leon, Sebastian |
| Publisher | STARS |
| Source Sets | University of Central Florida |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | Electronic Theses and Dissertations, 2020- |
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