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Title: Infection-responsive urinary biomaterials
Author: Irwin, Nicola Jayne
Awarding Body: Queen's University Belfast
Current Institution: Queen's University Belfast
Date of Award: 2013
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The catheterised urinary tract constitutes an ideal niche for bacterial colonisation, with an estimated 80% of all nosocomial urinary infections attributed to the presence of an indwelling catheter. The present thesis describes the rational design and development of three novel drug delivery systems for application as infection-resistant catheter coatings, which respond to the alkaline conditions generated at the onset of urinary catheter infections by urease-producing pathogens, particularly Proteus mirabilis, via the release of drugs. Upon probing P. mirabilis biofilms with a pH microelectrode, values up to pH 10.12 were recorded directly within the biofilm micro environment. In addition to exploiting this pH elevation to act as a trigger for drug release, the effect of pH on quinolone antibacterial activity is reported herein. Specifically, bactericidal potency of the fluoroquinolone agents: norfloxacin and ciprofloxacin, against P. mirabilis was observed to increase with elevated pH, whereas high concentrations of nalidixic acid demonstrated bactericidal activity selectively in alkaline environments, in contrast to the characteristic 'paradoxical' survival of bacteria observed with high concentrations of this agent in acidic and neutral media. In the first drug delivery system developed herein, the inherent pH -dependent physicochemical properties of nalidixic acid were exploited by a novel, surface particulate localisation method to achieve up to 50-fold faster drug release at pH 9 , than at normal physiological urine pH values ranging from pH 5 to pH 7. In contrast to physical drug loading, the final two systems focused on chemical conjugation of nalidixic acid and surfactant moieties via labile ester bonds to hydrogel backbones. Release of the covalently attached agents was successfully delayed at pH 7 compared to the significantly faster rates of ester hydrolysis and subsequent release at pH 10. Comparative differences in the resistances to bacterial adherence relative to the control hydrogel were demonstrated depending on the specific conjugated agent.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available