Effect of Hierarchical Cluster Formation on the Viscosity of Concentrated Monoclonal Antibody Formulations Studied by Neutron Scattering
| Autor: | P. Douglas Godfrin, Yun Liu, Peter Falus, Jonathan Zarzar, Lionel Porcar, Norman J. Wagner, Isidro E. Zarraga |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
Structure formation
02 engineering and technology Neutron scattering 010402 general chemistry 01 natural sciences Light scattering Neutron spin echo Viscosity Materials Chemistry Cluster Analysis Humans Scattering Radiation Neutron Physical and Theoretical Chemistry Neutrons Scattering Chemistry Antibodies Monoclonal 021001 nanoscience & nanotechnology Small-angle neutron scattering 0104 chemical sciences Surfaces Coatings and Films Crystallography Chemical physics Immunoglobulin G 0210 nano-technology |
| Zdroj: | The Journal of Physical Chemistry B. 120:278-291 |
| ISSN: | 1520-5207 1520-6106 |
| DOI: | 10.1021/acs.jpcb.5b07260 |
| Popis: | Recently, reversible cluster formation was identified as an underlying cause of anomalously large solution viscosities observed in some concentrated monoclonal antibody (mAb) formulations, which poses a major challenge to the use of subcutaneous injection for some mAbs. A fundamental understanding of the structural and dynamic origins of high viscosities in concentrated mAb solutions is thus of significant relevance to mAb applications in human health care, as well as being of scientific interest. Herein, we present a detailed investigation of an IgG1-based mAb to relate the short-time dynamics and microstructure to significant viscosity changes over a range of pharmaceutically relevant physiochemical conditions. The combination of light scattering, small-angle neutron scattering, and neutron spin echo measurement techniques conclusively demonstrates that, upon addition of Na2SO4, these antibodies form strongly bound reversible dimers at dilute concentrations that interact with each other to form large, loosely bound, transient clusters when concentrated. This hierarchical structure formation in solution causes a significant increase in the solution viscosity. |
| Databáze: | OpenAIRE |
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