Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.268632
Title: Towards the controlled destabilisation of aggregates
Author: Welsh, Simon
Awarding Body: Durham University
Current Institution: Durham University
Date of Award: 2002
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Abstract:
Lipid based non-viral delivery systems are potentially of great importance to the development of an effective and versatile therapeutic gene treatment. Many difficulties are faced in designing efficient lipid based gene delivery systems and addressing the problem of endosomal escape is one key area where efficiency could be greatly improved Molecules aimed at inducing aggregate disruption in response to changes in pH, or metal ion concentration, have been synthesised. Series of compounds were prepared based on cationic 5-alkyl-2-methylaminoalkyl pyridine amphiphiles and amphiphilic C(_8)-C(_16) EDTA dialkylamides. The critical aggregation concentration of each species was measured and a series of experiments undertaken, designed to assess the extent of pH, or metal ion concentration, induced aggregate disruption effects. The experiments were carried out by including the molecules to be examined as small mole percent co-aggregates in micellar and liposome model systems. Each group of compounds appears to exhibit disruption effects on the more strongly ordered bilayer membrane systems, with the EDTA based compounds displaying the most consistent pH dependent disruption. However, the more dynamic micellar aggregate models were less sensitive to disruption using the particular observation method employed.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.268632  DOI: Not available
Keywords: Gene delivery Molecular biology Cytology Genetics Medicine Biochemistry
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