title: Effect of polyol sugars on the stabilization of monoclonal antibodies.
abstract: 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.
authors: Department of Chemistry and Applied Biosciences, ETH Zurich, Zurich, Switzerland.
authors: Lucrèce
authors: L
authors: Nicoud
authors: Department of Chemistry and Applied Biosciences, ETH Zurich, Zurich, Switzerland.
authors: Nicholas
authors: N
authors: Cohrs
authors: Department of Chemistry, University of Cambridge, Cambridge, UK.
authors: Paolo
authors: P
authors: Arosio
authors: UCB Pharma, Braine-l'Alleud, Belgium.
authors: Edith
authors: E
authors: Norrant
authors: Department of Chemistry and Applied Biosciences, ETH Zurich, Zurich, Switzerland. Electronic address: massimo.morbidelli@chem.ethz.ch.
authors: Massimo
authors: M
authors: Morbidelli
mesh_terms: D000911:Antibodies, Monoclonal / Q000737:chemistry*; D005079:Excipients / Q000737:chemistry*; D005990:Glycerol / Q000737:chemistry; D006358:Hot Temperature; D007074:Immunoglobulin G / Q000737:chemistry*; D008320:Maltose / Q000031:analogs & derivatives / Q000737:chemistry; D055550:Protein Stability; D058767:Protein Unfolding; D013012:Sorbitol / Q000737:chemistry; D013395:Sucrose / Q000737:chemistry; D013402:Sugar Alcohols / Q000737:chemistry
chemical_list: D000911:Antibodies, Monoclonal; D005079:Excipients; D007074:Immunoglobulin G; D013402:Sugar Alcohols; D013012:Sorbitol; D013395:Sucrose; D008320:Maltose; C003460:threitol; C010745:maltitol; D005990:Glycerol
keywords: Aggregation mechanism; Excipient; Formulation; Kinetic model; Protein unfolding; Therapeutic protein