Macromolecular antineoplastic iron and platinum co-ordination compounds

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dc.contributor.author Mukaya, Hembe Elie
dc.date.accessioned 2014-01-07T06:52:48Z
dc.date.available 2014-01-07T06:52:48Z
dc.date.issued 2014-01-07
dc.identifier.uri http://hdl.handle.net10539/13357
dc.description A thesis submitted to the Faculty of Science, University of the Witwatersrand, Johannesburg, in fulfillment of the requirements for the degree of Doctor of Philosophy of Science. Johannesburg, 2013 en_ZA
dc.description.abstract Chemotherapy, while representing a vital component of cancer treatment modalities, has so far not fulfilled basic expectations with unsatisfactory cure rates and frequent relapse due to limited effectiveness of the therapeutic drugs, severe side effects and resistance problems. The platinumcontaining drugs used in present clinical practice are no exception to this generalized finding. While highly effective against a small number of malignancies, they generally share in the deficiencies of other anticancer agents. To address this issue, intense research is being undertaken to develop novel platinum-compounds offering enhanced therapeutic effectiveness. To accomplish this, several new avenues of development are being pursued world-wide, and one of these involving the binding of monomeric anticancer drug systems to water-soluble, biocompatible and biodegradable polymeric carriers, was utilized in the current research. As part of the ongoing research, this dissertation demonstrates the preparation of several water-soluble polymeric carriers bearing pre-synthesized monomers aimed to anchor the platinum drug. The monomers of interest were aspartic acid, p-aminobenzoic acid and p-aminosalicylic acid derivatives; while the water-soluble carriers were polyaspartamides, prepared by an aminolytic ring-opening process of polysuccinimide. The platination agents were conjugated to the polymer backbone both via amine and via leaving-group ligands, such as dihydroxylato, dicarboxylato and carboxylatohydroxylato. In order to demonstrate the multidrug-binding capacity of the carriers, platinum complexes were co-conjugated to polymeric conjugates containing ferrocene. The in vitro studies against a human breast cancer (MCF-7) cell line showed IC50 values ranging from 48.92 μg.mL-1 to 281.37 μg.mL-1 for the platinum conjugates, 13.18 μg.mL-1 to 149.67 μg.mL-1 for ferrocene conjugates and 6.22 μg.mL-1 to 83.86 μg.mL-1 for platinum/ferrocene co-conjugates; and these values were on average 4 fold more active than the parent drug. The results of these preliminary tests provide proof of the principle that polymer-drug conjugates can play a role in future cancer therapy. en_ZA
dc.language.iso en en_ZA
dc.subject.lcsh Antineoplastic agents - Therapeutic use.
dc.subject.lcsh Cancer - Chemotherapy.
dc.subject.lcsh Platinum.
dc.title Macromolecular antineoplastic iron and platinum co-ordination compounds en_ZA
dc.type Thesis en_ZA


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