A Colloid Approach to Self-Assembling Antibodies

Nicholas Skar-Gislinge, Michela Ronti, Tommy Garting, Christian Rischel, Peter Schurtenberger, Emanuela Zaccarelli, Anna Stradner

Research output: Contribution to journalArticlepeer-review

25 Citations (SciVal)

Abstract

Concentrated solutions of monoclonal antibodies have attracted considerable attention due to their importance in pharmaceutical formulations; yet, their tendency to aggregate and the resulting high viscosity pose considerable problems. Here we tackle this problem by a soft condensed matter physics approach, which combines a variety of experimental measurements with a patchy colloid model, amenable of analytical solution. We thus report results of structural antibodies and dynamic properties obtained through scattering methods and microrheological experiments. We model the data using a colloid-inspired approach, explicitly taking into account both the anisotropic shape of the molecule and its charge distribution. Our simple patchy model is able to disentangle self-assembly and intermolecular interactions and to quantitatively describe the concentration-dependence of the osmotic compressibility, collective diffusion coefficient, and zero shear viscosity. Our results offer new insights on the key problem of antibody formulations, providing a theoretical and experimental framework for a quantitative assessment of the effects of additional excipients or chemical modifications and a prediction of the resulting viscosity.

Original languageEnglish
Pages (from-to)2394-2404
Number of pages11
JournalMolecular Pharmaceutics
Volume16
Issue number6
DOIs
Publication statusPublished - 2019

Subject classification (UKÄ)

  • Pharmaceutical Sciences

Keywords

  • antibodies
  • patchy colloids
  • self-assembly

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