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Feasibility Testing of a New Nanotherapy for Ovarian Cancer / DENISE MEIJER

Swansea University Author: DENISE MEIJER

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Abstract

Currently the primary treatment of ovarian cancer (OC) is surgery with chemotherapy. Chem-otherapy is effective but platinum-based drugs commonly employed for OC, function with a specific mode of action, and are prone to adverse side effects and drug resistance, limiting the efficacy of the therapy....

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Published: Swansea 2022
Institution: Swansea University
Degree level: Master of Research
Degree name: MSc by Research
Supervisor: Godfrey, Ruth ; Francis, Lewis
URI: https://cronfa.swan.ac.uk/Record/cronfa59979
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first_indexed 2022-05-09T08:16:15Z
last_indexed 2022-05-10T03:33:13Z
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spelling 2022-05-09T09:32:58.1409438 v2 59979 2022-05-09 Feasibility Testing of a New Nanotherapy for Ovarian Cancer 6d49c62920f7abf7fd42cabb6d3bbc43 DENISE MEIJER DENISE MEIJER true false 2022-05-09 Currently the primary treatment of ovarian cancer (OC) is surgery with chemotherapy. Chem-otherapy is effective but platinum-based drugs commonly employed for OC, function with a specific mode of action, and are prone to adverse side effects and drug resistance, limiting the efficacy of the therapy.[1] BAY-784 is a GnRH-R antagonist which offers significant potential as an alternative therapy by functioning through alternative biochemical pathway, limiting cell replication by inhibiting growth hormones. However, this mechanism of action for OC is less well-defined in comparison to platinum therapies, with antagonist and agonist effects observed when non-specific drug administration routes are used. Because of the toxicity levels of BAY-784, liposomes were used to encapsulate this drug and induce the activity of BAY-784 on can-cer cells. To monitor the drug, we have developed an LC-DAD quantitative method and evaluated the tripartite sample preparation approach to provide absolute values of encapsulation. This latter method has shown a need for further method development due to incompatibilities with the liposome design, following formation via Thin-Film Hydration. As such, the encapsulation ef-ficiency was determined using an NMR approach and calculated to be 40%. The successful liposomal BAY-784 drug was tested on OVCAR-3 and SKOV-3 ovarian cancer cell lines and showed improved efficacy as an encapsulated therapy. However, the MoA of liposomal BAY-784 has not been monitored yet, free BAY-784 has shown a different mode of action, when using cell painting, on SKOV-3 cells affecting mostly the nucleus. E-Thesis Swansea Nanotherapy, GnRH-R, BAY-784, Liquid Chromatography, Nanoencapsulation, Liposomes, Analytical Method, Sample Preparation, SPE, LLE 12 4 2022 2022-04-12 COLLEGE NANME COLLEGE CODE Swansea University Godfrey, Ruth ; Francis, Lewis Master of Research MSc by Research 2022-05-09T09:32:58.1409438 2022-05-09T09:11:51.6008515 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Medicine DENISE MEIJER 1 59979__24025__a3af58d8a8ed4c9f8a8bbf9c87013275.pdf De Meijer_Denise_MSc_Research_Thesis_Final_Redacted_Signature.pdf 2022-05-09T09:26:48.4063887 Output 4861235 application/pdf E-Thesis – open access true Feasibility Testing of a New Nanotherapy for Ovarian Cancer © 2022 by Denise De Meijer is licensed under a Creative Commons Attribution 4.0 International (CC BY 4.0) License. Third party content is excluded for use under the license terms. true eng https://creativecommons.org/licenses/by/4.0/
title Feasibility Testing of a New Nanotherapy for Ovarian Cancer
spellingShingle Feasibility Testing of a New Nanotherapy for Ovarian Cancer
DENISE MEIJER
title_short Feasibility Testing of a New Nanotherapy for Ovarian Cancer
title_full Feasibility Testing of a New Nanotherapy for Ovarian Cancer
title_fullStr Feasibility Testing of a New Nanotherapy for Ovarian Cancer
title_full_unstemmed Feasibility Testing of a New Nanotherapy for Ovarian Cancer
title_sort Feasibility Testing of a New Nanotherapy for Ovarian Cancer
author_id_str_mv 6d49c62920f7abf7fd42cabb6d3bbc43
author_id_fullname_str_mv 6d49c62920f7abf7fd42cabb6d3bbc43_***_DENISE MEIJER
author DENISE MEIJER
author2 DENISE MEIJER
format E-Thesis
publishDate 2022
institution Swansea University
college_str Faculty of Medicine, Health and Life Sciences
hierarchytype
hierarchy_top_id facultyofmedicinehealthandlifesciences
hierarchy_top_title Faculty of Medicine, Health and Life Sciences
hierarchy_parent_id facultyofmedicinehealthandlifesciences
hierarchy_parent_title Faculty of Medicine, Health and Life Sciences
department_str Swansea University Medical School - Medicine{{{_:::_}}}Faculty of Medicine, Health and Life Sciences{{{_:::_}}}Swansea University Medical School - Medicine
document_store_str 1
active_str 0
description Currently the primary treatment of ovarian cancer (OC) is surgery with chemotherapy. Chem-otherapy is effective but platinum-based drugs commonly employed for OC, function with a specific mode of action, and are prone to adverse side effects and drug resistance, limiting the efficacy of the therapy.[1] BAY-784 is a GnRH-R antagonist which offers significant potential as an alternative therapy by functioning through alternative biochemical pathway, limiting cell replication by inhibiting growth hormones. However, this mechanism of action for OC is less well-defined in comparison to platinum therapies, with antagonist and agonist effects observed when non-specific drug administration routes are used. Because of the toxicity levels of BAY-784, liposomes were used to encapsulate this drug and induce the activity of BAY-784 on can-cer cells. To monitor the drug, we have developed an LC-DAD quantitative method and evaluated the tripartite sample preparation approach to provide absolute values of encapsulation. This latter method has shown a need for further method development due to incompatibilities with the liposome design, following formation via Thin-Film Hydration. As such, the encapsulation ef-ficiency was determined using an NMR approach and calculated to be 40%. The successful liposomal BAY-784 drug was tested on OVCAR-3 and SKOV-3 ovarian cancer cell lines and showed improved efficacy as an encapsulated therapy. However, the MoA of liposomal BAY-784 has not been monitored yet, free BAY-784 has shown a different mode of action, when using cell painting, on SKOV-3 cells affecting mostly the nucleus.
published_date 2022-04-12T04:17:41Z
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score 11.013731

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