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Abstract
Ubiquitous in the plant kingdom, polyphenols are naturally occurring compounds containing one or more phenol groups, which are well-known for their antioxidant properties. A high dietary intake of polyphenols has been linked to a reduced incidence of a number of diseases including cancer, cardiovascular diseases, diabetes, osteoporosis and neurodegenerative diseases. Furthermore, in vitro and in vivo studies show polyphenols have potential as therapeutic agents with cardioprotective, antimicrobial, anticancer, neuroprotective, and antidiabetic effects demonstrated. Despite their impressive therapeutic effects, polyphenols suffer from a number of drawbacks including instability when exposed to light, heat and basic conditions; poor bioavailability; rapid metabolism; and poor membrane permeability.
Polymers and other macromolecules are well-known for their ability to stabilise and improve the bioavailability of therapeutic agents. A number of research groups have successfully used polymers to stabilise polyphenols, either via conjugation or direct polymerisation, but the end products are often either insoluble in water or have limited concentrations of polyphenols. This thesis presents two new techniques to address these issues: the introduction of aldehyde groups onto polymer chains to allow for greater grafting density of polyphenol polymer conjugates; and the preparation of water soluble polyphenol polymers.
Two flavonoids, catechin and quercetin, were grafted onto a number of aldehyde-functionalised polysaccharide polymers and the grafting density was able to be tuned up to functionalisation levels of 48%. All flavonoid polymer conjugates exhibited improved antioxidant capacity compared with non-functionalised polymers and significant anticancer activity was also demonstrated. Flavonoid polymer conjugates were developed that were cytotoxic to neuroblastoma cells but demonstrated no cytotoxicity to non-malignant cells.
Water soluble polymers were also developed from catechin and quercetin. The catechin polymers showed a substantial increase in antimicrobial activity compared with native catechin and also proved to be highly effective stabilising agents for silver nanoparticles. Silver nanoparticles prepared with catechin polymers exhibited strong antimicrobial activity against gram positive and gram negative bacteria and also demonstrated substantially enhanced antibiofilm activity.