A Colloid Approach to Self-Assembling Antibodies
Research output: Contribution to journal › Journal article › Research › peer-review
Standard
A Colloid Approach to Self-Assembling Antibodies. / Skar-Gislinge, Nicholas; Ronti, Michela; Garting, Tommy; Rischel, Christian; Schurtenberger, Peter; Zaccarelli, Emanuela; Stradner, Anna.
In: Molecular Pharmaceutics, Vol. 16, No. 6, 03.06.2019, p. 2394-2404.Research output: Contribution to journal › Journal article › Research › peer-review
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - A Colloid Approach to Self-Assembling Antibodies
AU - Skar-Gislinge, Nicholas
AU - Ronti, Michela
AU - Garting, Tommy
AU - Rischel, Christian
AU - Schurtenberger, Peter
AU - Zaccarelli, Emanuela
AU - Stradner, Anna
N1 - Publisher Copyright: © 2019 American Chemical Society.
PY - 2019/6/3
Y1 - 2019/6/3
N2 - 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.
AB - 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.
KW - antibodies
KW - patchy colloids
KW - self-assembly
UR - http://www.scopus.com/inward/record.url?scp=85066118810&partnerID=8YFLogxK
U2 - 10.1021/acs.molpharmaceut.9b00019
DO - 10.1021/acs.molpharmaceut.9b00019
M3 - Journal article
C2 - 31059276
AN - SCOPUS:85066118810
VL - 16
SP - 2394
EP - 2404
JO - Molecular Pharmaceutics
JF - Molecular Pharmaceutics
SN - 1543-8384
IS - 6
ER -
ID: 367842187