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Determining the influence of polymer architecture on the transfection efficiency of cationic polymers
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Floyd, Thomas (2021) Determining the influence of polymer architecture on the transfection efficiency of cationic polymers. PhD thesis, University of Warwick.
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Official URL: http://webcat.warwick.ac.uk/record=b3719270
Abstract
The aim of this thesis is to study the impact of complex polymeric architectures on the ability of a polymer to complex and transfect plasmid DNA. The materials synthesised are based on a poly(2-ethyl-2-oxazoline) macromonomer, highlighting the versatility of the polymer to form a wide variety of materials.
The first chapter focuses on the optimisation of the macromonomer synthesis, followed by its polymerisation to form bottlebrush polymer. Detailed understanding of the bottlebrush polymer synthesis and structure are gained before the polymers are hydrolysed to introduce ethylenimine residues within the structure. Further characterisation are undertaken to determine the structural effects of this hydrolysis procedure.
The second chapter uses the cationic bottlebrush polymers synthesised in the first chapter and evaluates their ability to complex pDNA. Once an optimal ratio between polymer and pDNA has been established and their complexation understood, the polymers is used to transfect a GFP expressing pDNA in mammalian cells and compared against linear controls to ascertain the influence of architecture on the transfection ability.
In the final chapter the macromonomer is used to synthesise alternative nanostructures, nanoparticles, by surfactant-free emulsion polymerisation. Adjusting the ratio between macromonomer and core-forming, hydrophobic comonomer results in a system easily tuned for the preparation of nanoparticles. Extensive experiments on the effect of comonomer choice and macromonomer ratio is undertaken. The particles are then exposed to hydrolysis conditions, followed by evaluation on their ability to complex pDNA.
Item Type: | Thesis (PhD) | ||||
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Subjects: | Q Science > QD Chemistry R Medicine > RB Pathology |
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Library of Congress Subject Headings (LCSH): | Gene therapy, Transfection, Polymeric drug delivery systems, Polymerization, Copolymers -- Synthesis | ||||
Official Date: | June 2021 | ||||
Dates: |
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Institution: | University of Warwick | ||||
Theses Department: | Department of Chemistry | ||||
Thesis Type: | PhD | ||||
Publication Status: | Unpublished | ||||
Supervisor(s)/Advisor: | Perrier, Sébastien | ||||
Format of File: | |||||
Extent: | 193 leaves : illustrations | ||||
Language: | eng |
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