A Colloid Approach to Self-Assembling Antibodies
(2019) In Molecular Pharmaceutics 16(6). p.2394-2404- 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... (More)
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.
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- author
- Skar-Gislinge, Nicholas ; Ronti, Michela ; Garting, Tommy LU ; Rischel, Christian ; Schurtenberger, Peter LU ; Zaccarelli, Emanuela and Stradner, Anna LU
- organization
- publishing date
- 2019
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- antibodies, patchy colloids, self-assembly
- in
- Molecular Pharmaceutics
- volume
- 16
- issue
- 6
- pages
- 11 pages
- publisher
- The American Chemical Society (ACS)
- external identifiers
-
- pmid:31059276
- scopus:85066118810
- ISSN
- 1543-8384
- DOI
- 10.1021/acs.molpharmaceut.9b00019
- language
- English
- LU publication?
- yes
- id
- 98961cbf-9159-4157-aaa1-609a7c92417f
- date added to LUP
- 2019-06-14 13:46:05
- date last changed
- 2024-09-19 00:10:04
@article{98961cbf-9159-4157-aaa1-609a7c92417f, abstract = {{<p>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.</p>}}, author = {{Skar-Gislinge, Nicholas and Ronti, Michela and Garting, Tommy and Rischel, Christian and Schurtenberger, Peter and Zaccarelli, Emanuela and Stradner, Anna}}, issn = {{1543-8384}}, keywords = {{antibodies; patchy colloids; self-assembly}}, language = {{eng}}, number = {{6}}, pages = {{2394--2404}}, publisher = {{The American Chemical Society (ACS)}}, series = {{Molecular Pharmaceutics}}, title = {{A Colloid Approach to Self-Assembling Antibodies}}, url = {{http://dx.doi.org/10.1021/acs.molpharmaceut.9b00019}}, doi = {{10.1021/acs.molpharmaceut.9b00019}}, volume = {{16}}, year = {{2019}}, }