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dc.contributor.advisorForbes, Robert T.
dc.contributor.advisorHulse, W.L.
dc.contributor.authorVaidilaite-Pretorius, Agita*
dc.date.accessioned2017-10-19T14:22:43Z
dc.date.available2017-10-19T14:22:43Z
dc.date.issued2013
dc.identifier.urihttp://hdl.handle.net/10454/13482
dc.description.abstractControl and analysis of protein aggregation is an increasing challenge to biopharmaceutical research and development. Therefore it is important to understand the interactions, causes and analysis of particles in order to control protein aggregation to enable successful biopharmaceutical formulations. This work investigates the role of different non-ionic surfactants on protein conformational stability, as assessed by HSDSC, and on protein size stability as assessed by Dynamic Light Scattering (DLS), HIAC and MFI. BSA and IgG2 were used as model proteins. Thermal unfolding experiments indicated a very weak surfactant-immunoglobulin IgG2 interaction, compared to much stronger interactions for the BSA surfactant systems. The DLS results showed that BSA and IgG2 with different surfactants and concentration produced different levels of particle size growth. The heat treatment and aging of samples in the presence of Tween 20, Tween 80, Brij 35 and Pluronic F-68 surfactants led to an increase in the populations of larger particles for BSA samples, whereas IgG2 systems did not notably aggregate under storage conditions MFI was shown to be more sensitive than HIAC technique for measuring sub-visible particles in protein surfactant systems. Heat treatment and storage stress showed a significant effect on BSA and IgG2 protein sub-visible particle size stability. This work has demonstrated that both proteins with different Tween 20, Tween 80, Brij 35 and Pluronic F-68 concentrations, have different level of conformational and size stability. Also aging samples and heating stress bears the potential to generate particles, but this depends on surfactant type. Poor predictive correlations between the analytical methods were determined.en_US
dc.language.isoenen_US
dc.rights<a rel="license" href="http://creativecommons.org/licenses/by-nc-nd/3.0/"><img alt="Creative Commons License" style="border-width:0" src="http://i.creativecommons.org/l/by-nc-nd/3.0/88x31.png" /></a><br />The University of Bradford theses are licenced under a <a rel="license" href="http://creativecommons.org/licenses/by-nc-nd/3.0/">Creative Commons Licence</a>.en_US
dc.subjectSurfactant; High Sensitivity Differential Scanning Calorimetry (HSDSC); Liquid Particle Counter (HIAC); Micro-flow Imaging (MFI); Aggregation; Protein stabilization; Protein conformational stability, Sub-visible particles; Antibody IgG2; Bovine serum albumin (BSA); Size distributionen_US
dc.titleMechanistic approaches towards understanding particle formation in biopharmaceutical formations. The role of sufactant type and level on protein conformational stability, as assessed by calorimetry, and on protein size stability as assessed by dynamic light scattering, micro flow imaging and HIACen_US
dc.type.qualificationleveldoctoralen_US
dc.publisher.institutionUniversity of Bradfordeng
dc.publisher.departmentFaculty of Life Sciencesen_US
dc.typeThesiseng
dc.type.qualificationnamePhDen_US
dc.date.awarded2013
refterms.dateFOA2018-07-29T01:31:29Z


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