Date of Award
Spring 2026
Document Type
Open Access Dissertation
Department
Biomedical Engineering
First Advisor
Robert Michael Gower
Abstract
Chronic traumatic encephalopathy (CTE) resulting from repeat traumatic brain injuries currently lacks any effective pharmaceutical treatment options with current treatment plans revolving around mitigation of the symptoms and cognitive decline caused by disease progression. Potential small molecular therapeutics are limited in their effectiveness due to difficulty in delivering them to the brain via traditional routes of entry (oral, topical, or intravenous). This work seeks to develop a platform capable of delivering small hydrophobic molecules to the brain from an intranasal administration and implement it with all-trans retinoic acid to protect brain health in the chronic phase of repeat traumatic brain injuries (rTBI). In service of that, a DOTAP:PLG nanoparticle platform was developed through a nanoprecipitation protocol where the properties of the protocol were tweaked to produce positively charged (48.8±8.2 mV) nanoparticles under 250 nm in diameter on average. These nanoparticles were confirmed to be mucoadhesive through in vitro and in vivo assays and found to be retained in mouse nasal passages for at least four days post administration. Further work demonstrated the ability of intranasally administered DOTAP:PLG nanoparticles to deliver a hydrophobic molecule to the brain and led to development of a rTBI model and treatment regime for the chronic phase of the rTBIs. The rTBIs caused loss of object location recognition in the mice that was reversed for those who received ATRA DOTAP:PLG nanoparticle treatment while mice receiving a DOTAP:PLG vehicle nanoparticles saw continued loss of object location recognition. Tissue histology revealed presence of damaged neurons in the motor vi cortex and somatosensory cortex alongside more prominent damage in the optical tract all of which is ameliorated by ATRA intervention. No demyelination was observed within this timeframe. On the cellular level, microglial presence was increased in the motor cortex, somatosensory cortex, and optical tracts of mice that received rTBIs though microglial presence was reduced upon ATRA intervention. Astrocyte populations in the optical tract were increased in the Vehicle group compared to both the no rTBI control mice and the ATRA group of mice. Thus, the work herein presents a novel platform of mucoadhesive nanoparticles that can deliver small hydrophobic molecules to the brain which upon application after rTBI can improve brain health and cognitive performance in mice.
Rights
© 2026, Nicholas Andrew Colonna
Recommended Citation
Colonna, N. A.(2026). Treatment of Chronic Traumatic Encephalopathy With Nanoparticles: Mucoadhesive Nanoparticles With ATRA Improve Brain Health and Cognitive Performance After Repeat Traumatic Brain Injuries. (Doctoral dissertation). Retrieved from https://scholarcommons.sc.edu/etd/8919