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Title: Cation-exchanged zeolites as novel storage materials of nitric oxide : therapeutic potential in biomedical applications
Author: Fox, Sarah
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2008
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Zeolites can be manipulated to produce materials with varying NO storage and release capacities. NO is liberated from these structures on contact with an aqueous environment, making them ideal candidates for the development of biocompatible coatings on medical devices. The first experimental chapter examines the effects of two cation-exchanged zeolites (Co2+ and Zn2+) and their ability to inhibit collagen-induced platelet aggregation of human platelets ex vivo. The optimisation of zeolite design was carried out by comparing the effects of several compositions of Co2+ and Zn2+ zeolites in different polymer binders (PTFE and PDMS) using NO electrode measurements, platelet aggregation studies and fixed wire myography. Zn2+ and Co2+ exchanged zeolites at high compositions of zeolite to the polymer binder had potent anti-platelet and smooth muscle-relaxing effects that were associated with high concentrations of NO released for approximately 1 hour. The anti-platelet effects lasted for up to 2 hours in PRP and washed platelets and were largely sGC-independent. The 50% Zn2+-exchanged zeolite in a PTFE binder had the most promising NO release characteristics for further investigation in different biological assays. Chapter 5 focuses on the effects of 50% Zn2+ exchanged zeolites on neutrophil activation through the effect of exposure of zeolites on neutrophil activation markers in isolated human neutrophils in vitro. Flow cytometric analyses of antibodies against neutrophil surface markers were investigated in the presence of the neutrophil activator, fMLP. The results revealed a concentration-dependent ‘priming’ effect of NO on neutrophil activation, indicating that high concentrations of NO have a pro-inflammatory effect in this assay. Cell viability was assessed in parallel using Annexin V/Propidium iodide staining. This revealed a small concentration-dependent, up-regulation in necrotic cell changes in neutrophils exposed to NO. Chapter 6 investigated the anti-bacterial effects of 50% Zn2+ zeolites against strains of Gram-negative and Gram-positive bacteria that are commonly found in nosocomial infections caused by medical devices. Results revealed impressive anti-bacterial properties of NO-loaded zeolites to all strains of bacteria studied over relatively short time-spans. The bactericidal effect was concentration-dependent highlighting a potential use of these materials as ex vivo anti-bacterial agents. The success of NO-releasing zeolites to produce effects in a number of different biological assays shows promise for the use of thee material as anti-thrombotic and anti-infective coatings for medical devices.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available