Silica nanoparticles as vehicles for therapy delivery in neurological injury

<p>Acrolein, a very reactive aldehyde, is a culprit in the biochemical cascade after primary, mechanical spinal cord injury (SCI), which leads to the destruction of tissue initially unharmed, referred to as "secondary injury". Additionally, in models of multiple sclerosis (MS) and some clinical research, acrolein levels are significantly increased. This aldehyde overwhelms the natural anti-oxidant system, reacts freely with proteins, and releases during lipid peroxidation (LPO), effectively regenerating its self. Due to its ability to make more copies of itself in the presence of tissue via lipid peroxidation, researchers believe that acrolein plays a role in the increased destruction of the central nervous system in both SCI and MS. Hydralazine, an FDA-approved hypertension drug, has been shown to scavenge acrolein, but its side effects and short half life at the appropriate dose for acrolein scavenging must be improved for beneficial clinical translation. Due to the inefficient delivery of therapeutic drugs, nanoparticles have become a major field of exploration for medical applications. Based on their material properties, they can help treat disease by delivering drugs to specific tissues, enhancing detection methods, or a mixture of both. Nanoparticles made from silica provide distinct advantages. They form porous networks that can carry therapeutic molecules throughout the body. Therefore, a nanomedical approach has been designed using silica nanoparticles as a porous delivery vehicle hydralazine. The silica nanoparticles are formed in a one-step method that incorporates poly(ethylene) glycol (PEG), a stealth molecule, directly onto the nanoparticles. As an additional avenue for study, a natural product in green tea, epigallocatechin gallate (EGCG), has been explored for its ability to react with acrolein, disabling its reactive capabilities. Upon demonstration of attenuating acrolein, EGCG's delivery may also be improved using the nanomedical approach. The nanoparticles' physical characteristics were characterized and their interactions <em>in vitro</em>were studied for cytotoxicity and potential activity in attenuating neuronal damage.</p>

Name thesis:degree_name

Doctor of Philosophy (PhD)

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Biomedical Engineering

Year

2014

Author dc:creator

• Schenk, Desiree

Contributors dc:contributor

• James F. Leary
• Riyi Shi
• Mary Wirth
• Alyssa Panitch

• Nanoscience and Nanotechnology

Repository record dc:identifier

https://docs.lib.purdue.edu/open_access_dissertations/360

OAI identifier oai:identifier

oai:docs.lib.purdue.edu:open_access_dissertations-1510