Improving prostamide anti-cancer activity through derivatization and micellar delivery / by David Halatek.
| Author/creator | Halatek, David author. |
| Other author | Burns, Colin Sanderson, degree supervisor. |
| Other author | East Carolina University. Department of Chemistry. |
| Format | Theses and dissertations |
| Publication | [Greenville, N.C.] : [East Carolina University], 2023. |
| Description | 1 online resource (59 pages) : illustrations (some color) |
| Supplemental Content | Access via ScholarShip |
| Subjects |
| Summary | 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, [delta]12,14 prostamide J2 (15d-[delta]12,14-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-[delta]12,14-PMJ₂ induces cell death in primary patient melanoma cells and thus may be a promising therapeutic. As 15d-[delta]12,14-PMJ₂ can be made by the condensation of ethanolamine with 15-deoxy, [delta]12,14 prostaglandin J₂ (15d-[delta]12,14-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-[delta]12,14-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-[delta]12,14-PMJ₂-Arvanil was not as cytotoxic as 15d-[delta]12,14-PMJ₂. It is possible that the bulkier functional group on the [alpha]-chain of the prostamide prevents transport into the cell the same way or to the same degree 15d-[delta]12,14-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-[alpha]-tocopherol polyethylene glycol 1000 succinate were investigated as drug carriers. |
| General note | Presented to the Faculty of the Department Chemistry |
| General note | Advisor: Colin Burns |
| General note | Title from PDF t.p. (viewed July 23, 2024). |
| Dissertation note | M.S. East Carolina University 2023. |
| Bibliography note | Includes bibliographical references. |
| Technical details | System requirements: Adobe Reader. |
| Technical details | Mode of access: World Wide Web. |
Availability
| Library | Location | Call Number | Status | Item Actions |
|---|---|---|---|---|
| Electronic Resources | Access Content Online | ✔ Available |