Abstract
Crohn’s disease and ulcerative colitis, collectively known as inflammatory bowel disease (IBD), are chronic inflammatory conditions associated with significant patient morbidity, with more than 6.8 million patients globally suffering from IBD complications. Local drug delivery to the colon is favourable for improving treatment efficacy and reducing systemic side effects associated with IBD treatment. Hydrogels are one of the most promising platforms for developing site-specific drug delivery systems due to their unique features in responses to endogenous or exogenous triggers. The main aim of this PhD thesis was to develop stimuli-responsive hydrogels that possessed the ability to limit the release of drugs in the upper part of the gastrointestinal tract (GIT), stomach and small intestine while improving drug payload in the colonic part of the GIT. The findings of this thesis demonstrated that the pH-responsive hydrogel with enzyme-labile crosslinking agent successfully formed dual-responsive hydrogel, showcasing the promising development of a novel drug delivery system for local delivery of poorly water-soluble drug, mesalamine, and could also be used to improve their bioavailability for the treatment of IBD. Increasing crosslinking agent density successfully formed a compact polymeric network possessing the ability to control the release of highly-water soluble drug, metronidazole, making them a promising platform for controlling the release of various water-soluble drugs. Furthermore, the incorporation of MMA successfully formed a tri-polymeric network, making it also a promising carrier for controlling the release of metronidazole and highlighting the potential of these carriers for enhanced drug delivery to the colon. The encapsulated hydrogel film into a gastro-resistant capsule shell highlights the effectiveness of capsule-hydrogel systems in modulating drug release, providing valuable insights for the designing and optimisation of such unique multiple (capsule-hydrogel delivery systems) tailored for the controlled release of various drugs and emphasise the potential of such carriers for improving drug delivery to the colonic part of GIT.Thesis embargoed until 31 July 2029.
| Date of Award | Jul 2024 |
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| Original language | English |
| Awarding Institution |
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| Sponsors | Jerash University |
| Supervisor | Colin McCoy (Supervisor) & Matthew Wylie (Supervisor) |