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PDF of thesis T13401 PDF of thesis T13401 - (5 M)
Title Characterising immunoglobulin-polysorbate interactions / by Ruairidh Gair Couston.
Name Couston, Ruairidh Gair .
Abstract Therapeutic proteins, such as immunoglobulins, are typically formulated with polysorbates as stabilisers. However, the nature of the immunoglobulin-polysorbate interaction, particularly at the solid-liquid interface, is poorly characterised. This thesis presents an investigation of immunoglobulin (mAb-1)-surfactant interaction in bulk solution with particular focus on the interaction at the solid-liquid interface. It was first established using isothermal titration calorimetry that no specific binding interaction between mAb-1 and surfactant in solution takes place. Furthermore, circular dichroism and differential scanning calorimetry showed surfactant inclusion had no effect on mAb-1 native structure or thermal stability. The adsorption/desorption of mAb-1 and the effect of polysorbate was quantified in real-time by total internal reflection fluorescence. MAb-1 desorption was dependent on polysorbate concentration, fatty acid tail group and point of injection relative to mAb-1. MAb-1 adsorption to a hydrophobic surface was significantly less than to a hydrophilic surface. Concomitant conformational changes to mAb-1 were not apparent upon adsorption to a hydrophilic surface but a varying degree of (Sb(B-sheet loss was observed upon adsorption to hydrophobic surfaces. This was corroborated by neutron reflectivity (NR) data which modelled a bilayer for mAb-1 adsorbed to a hydrophilic surface and a monolayer for mAb-1 adsorbed to a hydrophobic surface. These NR data suggested a range of mAb-1 orientations were adopted. This combination of orthogonal surface analytical techniques can build up a detailed molecular-level image of the adsorbed protein layer enabling rapid characterisation of protein surface adsorption which will improve bioprocess design and formulation.
Publication date 2013
Name University of Strathclyde. Strathclyde Institute of Pharmacy and Biomedical Sciences.
Thesis note Thesis PhD University of Strathclyde 2013 T13401
System Number 000002324

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