Phage therapy is the use of bacteriophages to treat bacterial infections. Once a prominent method of antibacterial therapy, phage therapy became almost forgotten following the discovery of antibiotics in 1928. The rising instance of antibiotic resistant bacteria in the last number of years has resulted in resurgence in interest in phage therapy. Research into delivery methods for bacteriophages has been very limited. Up to very recently, phages had only been delivered parentrally using crude and purified phage stocks and orally for gastrointestinal infections. In order for phage therapy to become suitable for use in mainstream medicine, suitable dosage forms and phage delivery platforms must be developed. This research project endeavoured to successfully formulate a model bacteriophage, T4 phage, into useful polymeric delivery systems, beginning with an alginate based microparticulate system. Bacteriophages were successfully stabilized within a Ca-alginate-trehalose system and m icroparticles were fully characterised. The release profi le of these m icroparticles suggest that they could be used to successfully treat gastrointestinal infections. The present study also devised a phage stable soluble microneedle system. It was found that increasing the trehalose concentration within the microneedles, improved rnicroneedle strength, as did the addition of a Poly (methyl vinayl ether-eo-maleic acid) backing layer. A poly(carbonate) hollow rnicroneedle system was used to successfully deliver phages both in vitro and in vivo using a rat model. This study was the first time that bacteriophages have been delivered transdermally in vivo. Aside from the development of bacteriophage delivery systems, novel work in the application of Phage-Antibiotic synergy (PAS) to E.co/i biofilrns was completed with extremely successful results. It was found that administering T4 bacteriophage in combination with the antibiotic Cefotaxime improved biofilrn eradication, compared to treatment with bacteriophage or antibiotic alone. This is the first time that PAS has been applied to a biofilm model.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:558175 |
| Date | January 2011 |
| Creators | Ryan, Elizabeth Michelle |
| Publisher | Queen's University Belfast |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
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