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Title: Phage-based therapy for nasal and respiratory infections
Author: Alfadhel, Munerah
Awarding Body: University of Strathclyde
Current Institution: University of Strathclyde
Date of Award: 2013
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The adoption of therapy based on bacteriophage for the reduction of harboured pathogens is limited by a lack of understanding regarding their formulation as medicines. The product must able to efficiently deliver phage without deterioration and since oral delivery results in the destruction of the lytic activity, a nasal delivery system was investigated. This thesis first describes the formulation of lyophilised nasal inserts carrying a bacteriophage selective for S. aureus, for the eradication of MRSA resident in the nose. Lyophilization of bacteriophages in 1 mL of 1-2% (w/v) hydroxypropyl methylcellulose (HPMC) with or without the addition of 1% (w/v) mannitol yielded nasal inserts composed of a highly porous leaflet-like matrix. The bacteriophage titre fell following lyophilization to 108 pfu per insert, then reduced 100- to 1000-fold over 6 to 12 months storage at 4 oC. The second part of this thesis presented a new phage bioprocess method which involved co-precipitation of a n aqueous mixture of phage and a crystallisable carrier (glutamine or glycine) is described. Inclusion of albumin or trehalose at 5% w/w during co-precipitation provided additional stabilization of the phage. In the third part of this thesis, a lipid vehicle (LamellasomesTM) as a carrier in pulmonary delivery for antibiotics and/or bacteriophage was characterised. We further investigated the potential for co-formulation of antibiotics or bacteriophage by dispersion into LMS and nebulization of aerosolized droplets. Patients with cystic fibrosis (CF) may harbour antibiotic-resistant, mucoid strains of Pseudomonas aeruginosa in the lung. Bacteriophages were carried with the bulk fraction, rather than being selectively carried in larger or smaller aerosols. Dilution of colistin or tobramycin into LMS increased the nebulized drug fraction deposited into stages 2-5. This suggests that the surface activity of the LMS facilitates the generation of smaller aerosol droplets during nebulization. In conclusion, the work reported in this thesis suggests that bacteriophages can be formulated in a stable preparation and therefore have a potential as an alternative therapeutic agent for treatment of resistant bacterial infection on mucous surfaces.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available