The manufacture and characterization of protein nanoclusters

dc.contributor.advisorJohnston, Keith P., 1955-
dc.contributor.advisorMaynard, Jennifer Anne, 1974-
dc.creatorDinin, Aileen Kathrynen
dc.date.accessioned2014-11-07T21:23:40Zen
dc.date.accessioned2018-01-22T22:27:08Z
dc.date.available2018-01-22T22:27:08Z
dc.date.issued2013-05en
dc.date.submittedMay 2013en
dc.date.updated2014-11-07T21:23:41Zen
dc.descriptiontexten
dc.description.abstractThe ability to formulate monoclonal antibodies at high concentration in a low-viscosity form is of broad interest in drug delivery, as monoclonal antibody-based drugs are now prescribed for cancer, autoimmune disorders, and many other diseases. Herein, we create highly concentrated antibody dispersions (up to 260 mg/mL) via three different methods, utilizing proline as an interacting depletant or trehalose as a non-interacting depletant. These dispersions are able to achieve viscosities an order of magnitude lower than similarly concentrated antibody solutions over a range of formulation pHs. When diluted, these antibody dispersions return to monomer. The proline acts to minimize protein zeta potential, thus reducing the electrostatic repulsion on the protein, even when formulated 3 pH units away from the antibody pI. In addition, it acts as a depletant, forcing the monomers into cluster via osmotic effectsen
dc.description.departmentChemical Engineeringen
dc.format.mimetypeapplication/pdfen
dc.identifier.urihttp://hdl.handle.net/2152/27207en
dc.subjectProteinen
dc.subjectMonoclonal antibodyen
dc.subjectFormulationen
dc.subjectExcipienten
dc.subjectViscosityen
dc.subjectEquilibriumen
dc.titleThe manufacture and characterization of protein nanoclustersen
dc.typeThesisen

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