A Colloid Approach to Self-Assembling Antibodies

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

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

124 Downloads (Pure)

Abstrakt

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.
OriginalsprogEngelsk
TidsskriftMolecular Pharmaceutics
Vol/bind16
Udgave nummer6
Sider (fra-til)2394-2404
Antal sider11
ISSN1543-8384
DOI
StatusUdgivet - 2019

Emneord

  • Antibodies
  • Self-assembly
  • Patchy colloids

Citationsformater