| dc.contributor.author | Nyren-Erickson, Erin Kathryn | |
| dc.description.abstract | In recent years the rising cost and increased regulation within the U.S. healthcare system have caused medical laboratory tests to become more costly and more frequently required. As a result, insurance premiums are rising, and small independent laboratories are threatened with closure as their already narrow margins dwindle. Concurrently, there have been several incidents of contaminants and impurities in pharmaceutical drugs causing hundreds of deaths and thousands of illnesses. These challenges substantiate the need for simple and cost-effective screening tests for the presence of disease biomarkers, as well as for contaminants and impurities present in pharmaceutical drugs. The following disquisition reports three independent studies, each with the development of simple screening tools as its objective. Paper 1 reports the use of fluorescent lipid nanoparticles (liposomes) to detect changes in the species and concentrations of glycosaminoglycans (GAGs) in solution. We conclude that the emission intensity from the present fluorophores changes in response to increasing concentrations of GAGs, and can distinguish between serum from a healthy patient and serum having the same GAG concentrations as an Alzheimer's disease patient (simulated). Paper 2 reports the use of lipid nanoparticles to detect dangerous over-sulfated contaminants in pharmaceutical heparin. We report that liposomes in the presence of heparin or over-sulfated contaminants and Mg2+ ions form aggregates, and the size and zeta potential of these aggregates is dependent on the heparin/contaminant present. Further, the variation in aggregate zeta potential varies significantly upon heparin contamination, and may be used to detect 0.5% contaminant by weight. Paper 3 reports a clinical study to validate the presence of ADAM 12 (a disintegrin and metalloproteinase) enzyme in urine as a biomarker for breast cancer detection and diagnosis, as well as to monitor the effects of tumor removal on the urinary levels of this enzyme. We find no significant differences between recently diagnosed cancer patients (having undergone no treatment for cancer) and age-matched controls having no cancer present. Significant increases in urinary ADAM 12 only occur following surgery. Overall, we conclude that it is unlikely that a screen for urinary ADAM 12 will be useful for the diagnosis of breast cancer. | en_US |
| dc.publisher | North Dakota State University | en_US |
| dc.rights | NDSU Policy 190.6.2 | |
| dc.title | In Vitro Detection of Disease Biomarkers and Drug Contaminants | en_US |
| dc.type | Dissertation | en_US |
| dc.date.accessioned | 2017-12-11T19:17:31Z | |
| dc.date.available | 2017-12-11T19:17:31Z | |
| dc.date.issued | 2013 | |
| dc.identifier.uri | https://hdl.handle.net/10365/27018 | |
| dc.description.sponsorship | National Institutes of Health (NIH) | en_US |
| dc.description.sponsorship | North Dakota State University. Pharmaceutical Sciences | en_US |
| dc.description.sponsorship | Sanford Health | en_US |
| dc.description.sponsorship | American Foundation for Pharmaceutical Education | en_US |
| dc.rights.uri | https://www.ndsu.edu/fileadmin/policy/190.pdf | |
| ndsu.degree | Doctor of Philosophy (PhD) | en_US |
| ndsu.college | Health Professions | en_US |
| ndsu.department | School of Pharmacy | en_US |
| ndsu.program | Pharmaceutical Sciences | |
| ndsu.advisor | Mallik, Sanku | |
