The use of medical devices in the urinary tract is limited by infection. Consequences of catheter-associated urinary tract infection include an increase in mortality, perhaps due to secondary bacteraemia and septicaemia is, as well as increased expenditure on the replacement of catheters. Infection with urease-producing bacteria such as Proteus mirablis results in hydrolysis of urea in ammonia and carbon dioxide, and precipitation of magnesium and calcium salts which can result in the blockage of urinary medical devices, resulting in urine bypassing the catheter. This thesis aims to present a proof-of-concept of a pH-triggered multilayer catheter coating, capable of reacting to the presence of infection In vivo to reduce bacterial adherence to a urinary biomaterial. The methyl methacrylate polymers, Eudragit Preparation 415SF and Eudragit L1OO, were investigated as potential urinary catheter coatings. Eudragit Preparation 415SF is soluble at pH values above pH 7. Eudragit L lOO is soluble at pH values above pH 6. It was hypothesised that the tell-tale increase in pH as a result of infection with urease-producing bacteria like P. mirabilis would trigger a shedding of these surface layers, reducing bacterial adherence. By loading these polymer coatings with antibacterial agents and functional excipients, active agent could be released into the surrounding area, providing a secondary means of reducing bacterial activity. Initial studies developed formulations of Eudragit Preparation 41SSF and Eudragit L100, loaded with levofloxacin or nalidixic acid as model antibiotics, that could be processed using bench-top hot-melt extruders. Drug release studies in phosphate buffered saline at pH values representative of healthy and infected urine (pH 6.2 and ph. 7.8, respectively) demonstrated the pH-responsive properties of these formulations. When challenged with bacteria in artificial urine, the response of these formulations to the pH change caused by infection with urease-producing bacteria was demonstrated, with significantly reduced bacterial adherence with levofloxacin-containing formulations.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:601122 |
| Date | January 2013 |
| Creators | Croskery, Andrew |
| Publisher | Queen's University Belfast |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
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