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Cyclic peptide : polymer conjugate nanotubes for drug delivery applications
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Hill, Sophie K. (2023) Cyclic peptide : polymer conjugate nanotubes for drug delivery applications. PhD thesis, University of Warwick.
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WRAP_Theses_Hill_2023.pdf - Submitted Version Embargoed item. Restricted access to Repository staff only until 5 June 2025. Contact author directly, specifying your specific needs. - Requires a PDF viewer. Download (134Mb) |
Official URL: http://webcat.warwick.ac.uk/record=b3941348
Abstract
The objective of this thesis is to develop a blueprint for cyclic peptide – polymer conjugate nanotubes designed as delivery vectors for hydrophobic anti-cancer compounds, in order to improve their aqueous solubility and activity. Cyclic Peptide Nanotubes have recently garnered interest due to their supramolecular assemblies which can be considered reversible, thus allowing a graduation between a nanosized particle, and a smaller entity capable of being readily cleared from the body. Additionally, the high aspect ratio of nanotubes makes them attractive due to a potential for greater cellular uptake and blood circulation times. Hence, it is felt that manipulation of these properties and loading with a drug, can afford a transport system that is potentially more advantageous compared to others used in the field.
Initially the work focuses on the synthetic pathway to generate peptide-polymer conjugate nanotubes that are selectively modified by 1 drug and 1 polymer each, with a number of different sequences and chemistries utilised. Following an evaluation of the pros vs cons for each methodology, the self-assembly in solution is observed by a number of scattering or separation techniques to understand typical morphological changes instructed by inclusion of drug or specific polymer. Subsequently, the in vitro properties are investigated, starting with the drug release profile which can be modulated according to chemical linker type and polymeric architecture, providing the first proof that these nanotubes have various points of tuneability. The nanotube morphology and drug release is found to have a direct impact on the in vitro toxicity and uptake on both 2D, and more complex 3D models.
Finally, the nanotubes were labelled with an NIR fluorophore for biological imaging in tumour bearing mice, with an overall assessment of circulation times and organ biodistribution. A final tumour efficacy study attempts to understand whether these materials can be applied in vivo with minimal toxicity, and potential of tumour regression behaviours. Overall, this thesis intends to make the initial evaluation as to whether these materials have true potential as delivery vectors and how their fundamental behaviours can be exploited.
Item Type: | Thesis (PhD) | ||||
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Subjects: | Q Science > QD Chemistry | ||||
Library of Congress Subject Headings (LCSH): | Nanotubes, Cyclic peptides, Conjugated polymers, Drug delivery systems | ||||
Official Date: | January 2023 | ||||
Dates: |
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Institution: | University of Warwick | ||||
Theses Department: | Department of Chemistry | ||||
Thesis Type: | PhD | ||||
Publication Status: | Unpublished | ||||
Supervisor(s)/Advisor: | Perrier, Sebastien | ||||
Format of File: | |||||
Extent: | xix, 149 pages : colour illustrations | ||||
Language: | eng |
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