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

Swansea University Author: DENISE MEIJER

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    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.

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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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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.[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.
Keywords: Nanotherapy, GnRH-R, BAY-784, Liquid Chromatography, Nanoencapsulation, Liposomes, Analytical Method, Sample Preparation, SPE, LLE
College: Swansea University Medical School