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Title: Covalent and non-covalent modification of Tobramycin for improved delivery to the CF lung
Author: Cunningham, Richard
Awarding Body: Queen's University Belfast
Current Institution: Queen's University Belfast
Date of Award: 2015
Availability of Full Text:
Full text unavailable from EThOS. Thesis embargoed until 01 Jul 2019
Tobramycin, an aminoglycoside, is one of the mainstay treatments for chronic infections of pseudomonas Aeruginosa within the CF lung to decrease the bacterial burden. In in vivo studies tobramycin is highly potent against P. Aeruginosa, however, when administered to the CF lung large dosages are required to reach near MIC concentrations due to poor penetration of the CF mucus. These high dosages required lead to unwanted side effects and with the poor penetration of the CF mucus, the full therapeutic potential of tobramycin is unfulfilled. The focus has therefore been around the development of methodologies to functionalise tobramycin in order to facilitate the enhanced delivery to the CF lung using either covalent of non-covalent modification. One issue of tobramycin is its poor solubility in the majority of molecular solvents; as such the solubility of tobramycin was investigated within a series of hydrophilic ionic liquids. The solubility study proved successful, in which it was demonstrated that hydrophilic ionic liquids can solubilise tobramycin to a high degree, far surpassing that of conventional molecular solvents. Attempts to functionalise tobramycin using either P(III) or P(IV) reagents proved troublesome with little success, however, selective modification of the primary amine of tobramycin was achieved through potentially labile carbamate linkers. Attempts to conjugate these analogues of tobramycin with a functionalised analogue of SLPI, devised to act as a delivery vector was unfortunately not successful
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available