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Title: Block copolymer nanoparticles prepared by RAFT aqueous polymerisation
Author: Morse, Charlotte
Awarding Body: University of Sheffield
Current Institution: University of Sheffield
Date of Award: 2017
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This thesis describes the reversible addition-fragmentation chain transfer (RAFT) polymerisation of block copolymer nanoparticles in water. Firstly, a water-soluble poly(glycerol monomethacrylate) (PGMA) macromolecular chain-transfer agent (macro-CTA) was synthesised via RAFT solution polymerisation in ethanol. The PGMA macro-CTA is then chain-extended with 2-hydroxypropyl methacrylate (HPMA) via RAFT aqueous dispersion polymerisation. Polymerisation-induced self-assembly (PISA) occurs under these conditions, where the miscible HPMA monomer polymerises to form an insoluble poly (2-hydroxypropyl methacrylate) block, thus driving in situ formation of spheres, worms or vesicles. These PGMA-PHPMA diblock copolymers are then chain-extended with benzyl methacrylate (BzMA) via 'seeded' RAFT aqueous emulsion polymerisation to prepare PGMA-PHPMA-PBzMA triblock copolymers. In Chapter Two, a series of model framboidal PGMA-PHPMA-PBzMA triblock copolymer vesicles are synthesised with excellent control over surface roughness. Transmission electron microscopy (TEM) and small-angle X-ray scattering (SAXS) were utilised to characterise these nanoparticles, which were subsequently used to stabilise n-dodecane emulsion droplets in water. The adsorption efficiency, Aeff, of the nanoparticles at the n-dodecane/water interface was determined as a function of increasing vesicle surface roughness using a turbidimetry assay. A strong correlation between surface roughness and Aeff was observed, with Aeff increasing from 36 % up to 94 %. This is a significant improvement in Pickering emulsifier efficiency compared to that reported previously for similar vesicles with smooth surfaces. In Chapter Three, a series of PGMA-PHPMA-PBzMA triblock copolymer worms and spheres are synthesised. For certain block compositions, highly anisotropic worm-like particles are obtained, which are characterised by SAXS and TEM. The design rules for accessing higher order morphologies (i.e. worms or vesicles) are briefly explored. Surprisingly, vesicular morphologies cannot be accessed by targeting longer PBzMA blocks - instead only spherical nanoparticles are formed. SAXS is used to rationalise these counter-intuitive observations, which are best explained by considering subtle changes in the relative enthalpic incompatibilities between the three blocks during the growth of the PBzMA block. Finally, these PGMA-PHPMA-PBzMA worms are evaluated as Pickering emulsifiers for the stabilisation of oil-in-water emulsions. Millimetre-sized oil droplets were obtained using low-shear homogenisation (hand-shaking) in the presence of 20 % vol. n-dodecane. In contrast, control experiments performed using PGMA-PHPMA diblock copolymer worms indicated that these more delicate nanostructures did not survive even these mild conditions. In the latter two experimental Chapters of this thesis, PISA is used to design block copolymer nanoparticles as potential drug delivery vehicles. Thus, PGMA-PHPMA diblock copolymer vesicles are prepared in the presence of varying amounts of silica nanoparticles of approximately 18 nm diameter. After centrifugal purification to remove excess non-encapsulated silica nanoparticles, analysis confirms encapsulation of up to hundreds of silica nanoparticles per vesicle. Silica is a model payload: it has high electron contrast compared to the copolymer and its thermal stability enables quantification of the loading efficiency via thermogravimetric analysis. Encapsulation efficiencies can be obtained using disk centrifuge photosedimentometry, since the vesicle density increases at higher silica loadings while the mean vesicle diameter remains essentially unchanged. SAXS is used to confirm silica encapsulation, because a structure factor is observed at q ~ 0.25 nm-1. A new two-population model provides satisfactory data fits to the SAXS patterns and allows the mean silica volume fraction within the vesicles to be determined. These silica-loaded vesicles constitute a useful model system for understanding the encapsulation of globular proteins, enzymes or antibodies within block copolymer vesicles for potential biomedical applications. They may also serve as an active payload for self-healing hydrogels or repair of biological tissue. Finally, by targeting a relatively short PHPMA block, PGMA-PHPMA vesicles can be obtained that lie close to the worm-vesicle phase boundary, rendering them thermo-responsive. The thermo-responsive nature of these vesicles enables thermally-triggered release of the encapsulated silica nanoparticles simply by cooling to 0-10oC, which induces a morphological transition. TEM studies confirm the change in diblock copolymer morphology and also enables direct visualisation of the released silica nanoparticles. Time-resolved small angle X-ray scattering is used to quantify the extent of silica release over time. For these experiments, the purified silica-loaded vesicles were cooled to 0oC for 30 min and SAXS patterns were collected every 15 s. For PGMA-PHPMA vesicles synthesised in the absence of silica nanoparticles, vesicles remained intact for 8 minutes before a vesicle-to-worm transition occurs. Thereafter, a worm-to-sphere transition occurs after 12 min at 0oC. For lower silica loadings, cooling induces a vesicle-to-sphere transition with subsequent nanoparticle release. For higher silica loadings, cooling to 0oC for 30 min only leads to perforation of the vesicle membranes, but silica nanoparticles are still released through the pores. For vesicles prepared in the presence of 30 % w/w silica, a new SAXS model has been developed to determine both the mean volume fraction of encapsulated silica remaining within the vesicles and also the scattering length density of the vesicle. Satisfactory data fits to the experimental SAXS patterns were obtained using this model. These results indicate that 68 % of the encapsulated silica is released from the vesicles after being held at 0°C for 30 min.
Supervisor: Armes, Steven Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available