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Effect of polyol sugars on the stabilization of monoclonal antibodies.
Journal article

Effect of polyol sugars on the stabilization of monoclonal antibodies.

  • Nicoud L Department of Chemistry and Applied Biosciences, ETH Zurich, Zurich, Switzerland.
  • Cohrs N Department of Chemistry and Applied Biosciences, ETH Zurich, Zurich, Switzerland.
  • Arosio P Department of Chemistry, University of Cambridge, Cambridge, UK.
  • Norrant E UCB Pharma, Braine-l'Alleud, Belgium.
  • Morbidelli M Department of Chemistry and Applied Biosciences, ETH Zurich, Zurich, Switzerland. Electronic address: massimo.morbidelli@chem.ethz.ch.
  • 2015-02-04
Published in:
  • Biophysical chemistry. - 2015
Aggregation mechanism
Excipient
Formulation
Kinetic model
Protein unfolding
Therapeutic protein
Antibodies, Monoclonal
Excipients
Glycerol
Hot Temperature
Immunoglobulin G
Maltose
Protein Stability
Protein Unfolding
Sorbitol
Sucrose
Sugar Alcohols
English We investigate the impact of sugars and polyols on the heat-induced aggregation of a model monoclonal antibody whose monomer depletion is rate-limited by protein unfolding. We follow the kinetics of monomer consumption by size exclusion chromatography, and we interpret the results in the frame of two mechanistic schemes describing the enhanced protein stability in the presence of polyols. It is found that the stabilization effect increases with increasing polyol concentration with a comparable trend for all of the tested polyols. However, the stabilization effect at a given polyol concentration is polyol specific. In particular, the stabilization effect increases as a function of polyol size until a plateau is reached above a critical polyol size corresponding to six carbon atoms. Our results show that the stabilization by polyols does not depend solely on the volume fraction filled by the polyol molecules, but is also affected by the polyol chemistry.
Language
  • English
Open access status
closed
Identifiers
Persistent URL
https://folia.unifr.ch/global/documents/153509
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