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Title: Nanoparticulate copolymers for the encapsulation and release of bioactive molecules
Author: Sommer, Katherine
Awarding Body: University of Reading
Current Institution: University of Reading
Date of Award: 2013
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Three nanoparticle systems were investigated for the nano-encapsulation and release of bioactive molecules. The first series of hydroxyethyl methacrylate-co-carboxyethyl acrylate random polymers were found, above their critical aggregation concentration (CAC), to self-assemble into spherical nanoparticles which dissociated when the external pH rose above 4. The second and third series were core:shell microgels, crosslinked with ethylene glycol dimethacrylate (EGDMA), made from a core composed of hydroxyethyl methacrylate (HEMA) and a carboxyethyl acrylate (CEA) shell which underwent volume transitions when the external solution was raised above pH 4. These nanoparticle systems were investigated using proton NMR, zeta-potential, dynamic light scattering (DLS), potentiometric titrations, gel permeation chromatography (GPC) and turbidity studies. The shape, morphology and core:shell architecture were imaged using transmission electron microscopy (TEM) staining with uranyl acetate and phosphotungstic acid (PTA), Cryo-TEM, scanning electron microscopy (SEM), cryo-SEM, confocal microscopy and optical microscopy. The micro gels were all shown to have good biocompatibility by slug mucosal tests. The uptake and release of three dyes; Rhodamine 6G, Coumarin 153, and 9-diethylamino-5-benzo[a]phenoxazinone (Nile red) were investigated. High uptake of the dye molecules was observed at pH 4 and high release at pH 7, with microgel particle separation from the aqueous solution being achieved by centrifugation. The micro gel systems were investigated for the uptake of the model pharmaceuticals paracetamol, caffeine, dopamine, ibuprofen, carbamazepine and riboflavin; all of which have been detected globally in drinking water supplies. The uptake of pharmaceuticals by the microgel systems was shown to be low at both pH 4 and pH 7. The low uptake was concluded to be caused by the carboxylic acids groups localised on the microgel surface creating a collapsed skin layer, so inhibiting the inward diffusion of additional drugs. The uptake and release experiments were performed using spectrofluorescence analysis and UV -visible spectrometry. All three nanoparticulate systems were filterable from aqueous media at low (15 psi) pressure using lab-cast polyethersulphone (PES) ultrafiltration membranes with a molecular weight cut off (MWCO) of 10kDa.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available