Use of Inorganic Polymers as a Delivery Vehicle for Bioinorganic Anticancer Drugs

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dc.contributor.advisor Leitao, E en
dc.contributor.advisor Hartinger, C en Shaheem, Shaheena en 2018-08-01T22:00:13Z en 2018 en
dc.identifier.uri en
dc.description Full text is available to authenticated members of The University of Auckland only. en
dc.description.abstract Like tamoxifen, its ferrocene-based analogue ferrocifens have shown promising anti-proliferative activities in various cancer cells, especially in oestrogen-dependent and –independent breast cancer cells. However, ferrocifens have poor solubility in aqueous media due to their high hydrophobicity inherent in the structure and this has prevented them from entering clinical trials. This issue is an important one to address because chemotherapy drugs need to have adequate hydrophilicity in order to be soluble in aqueous blood and plasma media. To improve the delivery of ferrocifens, this project aimed to design a drug delivery system based on attaching these drugs to a polymer. Such macromolecules can pass through the gaps between endothelial cells in tumour blood vessels via the enhanced permeability and retention (EPR) effect. Polyphosphazenes, the polymer of choice, have been previously employed as a polymeric support for biologically active agents, such as drug, tissue, gene, etc. due to its broad structural diversity and biocompatibility. The project aimed to synthesise, and then link ferrocifen drugs to polyphosphazene through cleavable linkers. The resulting drug delivery system could then be used for targeted delivery and controlled release of the drug in cancer cells. Once in the cancer cell, the linker can be cleaved by biological stimuli, such as low pH, hypoxia, etc., releasing the active ferrocifen. As part of the drug delivery system, the syntheses of ferrocifen compounds and polyphosphazenes were the attempted first. For the synthesis of ferrocifen compounds, Fc-diOH was successfully synthesised and characterised. However, during the attempt of synthesising Fc-OH-Tam, a novel ferrocifen compound may have been synthesised instead. Synthesis of polyphosphazenes using thermal ring opening polymerisation and living cationic polymerisation were attempted. A range of model conditions were performed to determine the most optimal conditions for linking ferrocifen drug to 1-azido-3- iodopropane linker. Coupling between ferrocifen and azide linker, and substitution of 3-butyn-1-ol linker on hexachlorocyclotriphosphazene (as a model for polyphosphazenes) were also attempted. In addition, conjugation of hexachlorocyclotriphosphazene to the drug were attempted using a model system. en
dc.publisher ResearchSpace@Auckland en
dc.relation.ispartof Masters Thesis - University of Auckland en
dc.relation.isreferencedby UoA99265071911702091 en
dc.rights Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. en
dc.rights Restricted Item. Available to authenticated members of The University of Auckland. en
dc.rights.uri en
dc.rights.uri en
dc.title Use of Inorganic Polymers as a Delivery Vehicle for Bioinorganic Anticancer Drugs en
dc.type Thesis en Chemistry en The University of Auckland en Masters en
dc.rights.holder Copyright: The author en
pubs.elements-id 750670 en
pubs.record-created-at-source-date 2018-08-02 en

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