A Colloid Approach to Self-Assembling Antibodies

Research output: Contribution to journalJournal articleResearchpeer-review

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

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
JournalMolecular Pharmaceutics
Volume16
Issue number6
Pages (from-to)2394-2404
Number of pages11
ISSN1543-8384
DOIs
Publication statusPublished - 3 Jun 2019
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2019 American Chemical Society.

    Research areas

  • antibodies, patchy colloids, self-assembly

ID: 367842187