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Design and synthesis of responsive nanoparticles for targeted drug delivery
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Richardson, Robert A. E. (2020) Design and synthesis of responsive nanoparticles for targeted drug delivery. PhD thesis, University of Warwick.
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WRAP_Theses_Richardson_2020.pdf - Submitted Version - Requires a PDF viewer. Download (3652Kb) | Preview |
Official URL: http://webcat.warwick.ac.uk/record=b3692502~S15
Abstract
Cancer is the second leading cause of death globally. Although many small molecule anti-cancer drugs have been developed, they suffer from several shortcomings. Most visibly, the poor targeting of small molecule drugs can cause side effects such as hair and muscle loss, and damage to the stomach lining. Small molecule drugs are also exposed to metabolic and clearance pathways, reducing overall efficiencies and requiring an even larger dose of these effectively toxic drugs to be administered. Small molecule drugs must also be soluble in the aqueous environment of the body; precluding the use of very hydrophobic molecules. A promising solution to these problems is to encapsulate small molecule drugs within a polymeric nanoparticle delivery vehicle. The polymer shell can help solubilise the drug, shield it from metabolic damage and enable transport to the tumour. However, it is vital to release the drug on demand from the particle and avoid any potentially toxic accumulation of the particles once delivery is complete. This thesis aims to investigate the synthesis of responsive polymeric nanoparticles and their potential applications to drug delivery systems. These nanoparticles are comprised of low dispersity polymers, expected to have similar biological properties, prepared by Reversible Addition Fragmentation chain Transfer (RAFT) polymerisation. While RAFT and emulsion polymerisation have been successfully combined to produce nanoparticles in the past, it has proven difficult to produce both low dispersity polymers and particles. Herein the effect emulsion polymerisation setup has on RAFT controlled is extensively explored. It is shown that RAFT control over the polymerisation of acrylates and methacrylates is improved substantially by emulsion polymerisation. The origin of this control is investigated and shown to be a consequence of the in-built monomer feeding mechanism existent within emulsion polymerisation. The improvement in RAFT control is utilised to produce multiblock copolymer particles.
Item Type: | Thesis (PhD) | ||||
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Subjects: | R Medicine > RS Pharmacy and materia medica | ||||
Library of Congress Subject Headings (LCSH): | Nanoparticles -- Synthesis, Drug carriers (Pharmacy), Polymeric drug delivery systems | ||||
Official Date: | December 2020 | ||||
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 | ||||
Sponsors: | Engineering and Physical Sciences Research Council ; Lubrizol Corporation ; Royal Society of Chemistry (Great Britain) ; Society of Chemical Industry (Great Britain) ; Cancer Research UK | ||||
Format of File: | |||||
Extent: | 142 leaves : illustrations (some colour) | ||||
Language: | eng |
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