Improving Prostamide Anti-Cancer Activity Through Derivatization and Micellar Delivery
dc.contributor.author | Halatek, David James | |
dc.contributor.department | Chemistry | |
dc.date.accessioned | 2023-06-05T13:54:11Z | |
dc.date.available | 2023-06-05T13:54:11Z | |
dc.date.created | 2023-05 | |
dc.date.issued | 2023-04-28 | |
dc.date.submitted | May 2023 | |
dc.date.updated | 2023-06-02T15:40:51Z | |
dc.degree.department | Chemistry | |
dc.degree.discipline | MS-Chemistry | |
dc.degree.grantor | East Carolina University | |
dc.degree.level | Masters | |
dc.degree.name | M.S. | |
dc.description.abstract | Colorectal cancer is the fourth most common cancer diagnosis per year as well as the fourth highest rate of death per year according to the Centers for Disease Control. Approximately 1/3rd of the diagnosed colorectal cancer cases per year will result in death. Prior research from our group has shown that the prostaglandin-ethanolamide 15-deoxy, D12,14 prostamide J2 (15d-D12,14-PMJ2) is selectively toxic to murine melanoma cells (B16F10) and murine colorectal cells (CT-26) both in vitro and in vivo and significantly reduces tumor growth. Further, 15d-D12,14-PMJ2 induces cell death in primary patient melanoma cells and thus may be a promising therapeutic. As 15d-D12,14-PMJ2 can be made by the condensation of ethanolamine with 15-deoxy, D12,14 prostaglandin J2 (15d-D12,14-PGJ2), we sought to test the cytotoxicity of other prostamide derivatives to determine the structural features required for activity. Based on prior results in a study of related prodrugs, 15d-D12,14-PMJ2-Arvanil was selected as the top candidate for testing anti-cancer activity. After testing in both a human and murine cell line, it was determined that 15d-D12,14-PMJ2-Arvanil was not as cytotoxic as 15d-D12,14-PMJ2. It is possible that the bulkier functional group on the α-chain of the prostamide prevents transport into the cell the same way or to the same degree 15d-D12,14-PMJ2 enters. In an effort to test this hypothesis, and to develop an improved means for systemic delivery for this class of hydrophobic prostamides, engineered micelles composed of 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000] and D-α-tocopherol polyethylene glycol 1000 succinate were investigated as drug carriers | |
dc.format.mimetype | application/pdf | |
dc.identifier.uri | http://hdl.handle.net/10342/12851 | |
dc.language.iso | en | |
dc.publisher | East Carolina University | |
dc.subject | Cancer Therapeutics | |
dc.subject | Cancer Treatments | |
dc.subject | Small Molecule | |
dc.subject | Cancer | |
dc.subject | Prostamide | |
dc.subject | Anandamide | |
dc.subject | Prostaglandin | |
dc.subject | J-series Prostaglandins | |
dc.subject | J-series | |
dc.title | Improving Prostamide Anti-Cancer Activity Through Derivatization and Micellar Delivery | |
dc.type | Master's Thesis | |
dc.type.material | text |
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