Date of Graduation

5-2020

Document Type

Thesis

Degree Name

Bachelor of Science

Degree Level

Undergraduate

Department

Chemistry & Biochemistry

Advisor/Mentor

Tian, Ryan

Committee Member/Reader

Jensen, Hannah

Committee Member/Second Reader

Sakon, Joshua

Committee Member/Third Reader

Thallapuranam, Suresh

Abstract

Amyotrophic lateral sclerosis (ALS) is a progressive, fatal neurodegenerative disorder characterized in pathology by a significant loss of upper and lower motor neurons, leading to muscle wasting and loss of voluntary movement. There are about 6,000-8,000 new cases of ALS diagnosed per year in the U.S., with a fatal outcome within 2 to 4 years (on average) after diagnosis. There are only two FDA approved drugs for treating ALS. Both are very expensive and only have modest benefits for patients. The population is in dire need of more affordable and effective medicine for the treatment of ALS.

Therefore, the goal of this research was to test the viability of alginate nanofibers cross-linked to non-toxic levels of calcium, barium, and strontium for the release of methylene blue as a potential novel drug delivery system for the treatment of ALS. Alginate possesses antioxidant activity, immunoregulatory activity, anti-inflammatory activity, and neuroprotective activity. Methylene blue also possesses antioxidant activity and has been shown to inhibit aggregation of TDP43, a protein that is aggregated in up to 97% of all ALS patients. These properties, in combination, would have great advantages for mitigating the multi-faceted pathogenesis of amyotrophic lateral sclerosis.

The nanofibers were synthesized using immersive rotary jet spinning followed by lyophilization. Various concentrations (50 mM, 100 mM, 200 mM, 300 mM, and 400 mM) of cross-linking cation were used to cross-link with 1% w/v alginate solution. Release studies with methylene blue occurred over a three-hour time period. Data were collected on the loading efficiencies, release profiles, and degradation times of the nanofibers using UV-Vis spectroscopy. Strontium 300 mM loaded with 31.2 μL of methylene blue had the highest loading efficiency at 59.9%. This nanofiber also loaded the most moles per milligram of nanofiber at 2.9 nanomoles/mg. Barium alginate nanofibers had the highest structural integrity followed by strontium then calcium. The release kinetics of the nanofibers were inconclusive due to high error associated with each time point potentially due to redox reactions between alginate and methylene blue.

Keywords

nanofibers; alginate; methylene blue; nanoscaffold; ALS; Amyotrophic Lateral Sclerosis

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