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Title: Reversible addition-fragmentation chain transfer emulsion polymerisation for preparation of biologically compatible nanoparticles
Author: Gurnani, Pratik
ISNI:       0000 0004 8497 6093
Awarding Body: University of Warwick
Current Institution: University of Warwick
Date of Award: 2018
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Reversible deactivation radical polymerisation represents a versatile route to prepare well-defined polymeric materials with complex architecture, controlled molecular weight and tuneable end-groups. RDRP techniques have now been translated to heterogeneous polymerisations (emulsion, dispersion, suspension etc.) allowing large scale preparation of nanoparticles with tuneable cores and shells in an aqueous environment. Such systems show great promise in biomedical applications due to their long circulation time, passive tumour accumulation, and core-shell architecture capable of drug loading and controlled release. The overall aim of this thesis is to assess RAFT emulsion polymerisation as a route to prepare nanoparticles for potential biomedical applications, and to study their physical properties, cytotoxicity, cellular uptake and in vivo distribution. Firstly, the synthesis of nanoparticles from amphiphilic block copolymers via RAFT emulsion polymerisation is explored, revealing optimum conditions. Preliminary in vitro and in vivo cytotoxicity and biodistribution studies indicated high biocompatibility with significant liver accumulation post-injection. Following this, a systematic study identifying the effect of nanoparticle rigidity on cellular uptake is explored using a library of hard, intermediate or soft cores tuned with their glass transition temperature. Intracellular fluorescence studies display an increasing amount of uptake with decreasing nanoparticle rigidity, with mechanistic studies suggesting this could be due to a preference of the harder nanoparticles to be internalised via clathrin and caveolae-mediated endocytosis. In the next chapter, alkyne functional RAFT agents are prepared to impart functionality at the nanoparticle surface. It is found that by replacing the initial carboxylate with other functionality significantly reduces colloidal stability. Finally, polysulfonated macro-RAFT agents are used to synthesise heparin-mimicking nanoparticles, via RAFT emulsion polymerisation, capable of stabilising growth factors. The nanoparticles outperform linear analogues and heparin itself, suggesting that the high local concentration at the particle surface significantly improves bioactivity. Overall, this thesis describes how aspects such as particle size, core and shell composition, and corona functionality can be modified individually for specific biological applications.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: QD Chemistry