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Investigating Nonlinear Enzyme Kinetics as an Internal Control System for Nanoreactor Drug Release

Jones, Stephen Joseph (2018) Investigating Nonlinear Enzyme Kinetics as an Internal Control System for Nanoreactor Drug Release. PhD thesis, University of Leeds.

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Abstract

The improper administration of therapeutic compounds is not only financially inefficient, but, there exists a very real risk of harmful, or potentially life-threatening effects. To gain control, nano-drug delivery systems provide a discernible option for temporal and spatial regulation of drug bioavailability within the body. In current regimes, temporal control is realised through gradual release over an extended period of time, or triggered release in response to a change in the physiochemical environment. Of course, when considering the design of an ideal drug delivery system, we think of adaptivity – adaptivity to dynamically modulate drug release in response to a changing biological macroenvironment. In nature, this ability to sense, communicate, and respond is fundamental to the existence of any living organism, irrespective of complexity. In most instances, this responsiveness is achieved through feedback-controlled biochemical processes that work to regulate a functional process, and so, any “smart” delivery system would be smart to do the same. Of course, where conventional chemical feedback is concerned, potential toxicity and lack of biocompatibility, caused by inappropriate catalysts, is problematic, however, the emergence and enhanced understanding of enzymatic feedback provides an interesting and more compatible alternative. As such, this doctoral thesis focuses on drawing together two distinct entities of intense scientific focus, nonlinear enzyme kinetics and nanoreactor technology, and works towards the idealism of a feedback-controlled secondary response. To achieve this, through the utilisation of bottom-up synthetic chemistry, we have successfully built, investigated, and optimised a platform that has allowed up to systematically and extensively investigate the effect of confinement on an enzymatic feedback reaction. Through this process, we have uncovered a system more complicated than first anticipated. This complexity, driven firstly by the fragility of constituents in relatively harsh conditions, but more importantly by the dynamism of the system in terms of membrane transport, and associated pH-linked permeability coefficients. However, by building this platform, we have not only learned how to control the kinetic output of the reaction, but have gained an overview of how the system behaves as a whole. It is this organic discovery, and ultimate understanding, that has allowed us to extend our reach, pushing the functionality of our novel system, to achieve both temporally-controlled drug delivery and nano-motor-based vesicular propulsion.

Item Type: Thesis (PhD)
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Keywords: nanoreactor nonlinear urease oscillations feedback drug delivery vesicles liposomes
Academic Units: The University of Leeds > Faculty of Maths and Physical Sciences (Leeds) > School of Chemistry (Leeds)
Depositing User: Dr Stephen Joseph Jones
Date Deposited: 04 Dec 2018 11:13
Last Modified: 04 Dec 2018 11:13
URI: http://etheses.whiterose.ac.uk/id/eprint/22207

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