A Colloid Approach to Self-Assembling Antibodies

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

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Resumé

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

Citer dette

Skar-Gislinge, N., Ronti, M., Garting, T., Rischel, C., Schurtenberger, P., Zaccarelli, E., & Stradner, A. (2019). A Colloid Approach to Self-Assembling Antibodies. Molecular Pharmaceutics, 16(6), 2394-2404. https://doi.org/10.1021/acs.molpharmaceut.9b00019
Skar-Gislinge, Nicholas ; Ronti, Michela ; Garting, Tommy ; Rischel, Christian ; Schurtenberger, Peter ; Zaccarelli, Emanuela ; Stradner, Anna. / A Colloid Approach to Self-Assembling Antibodies. I: Molecular Pharmaceutics. 2019 ; Bind 16, Nr. 6. s. 2394-2404.
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title = "A Colloid Approach to Self-Assembling Antibodies",
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.",
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Skar-Gislinge, N, Ronti, M, Garting, T, Rischel, C, Schurtenberger, P, Zaccarelli, E & Stradner, A 2019, 'A Colloid Approach to Self-Assembling Antibodies', Molecular Pharmaceutics, bind 16, nr. 6, s. 2394-2404. https://doi.org/10.1021/acs.molpharmaceut.9b00019

A Colloid Approach to Self-Assembling Antibodies. / Skar-Gislinge, Nicholas; Ronti, Michela; Garting, Tommy; Rischel, Christian; Schurtenberger, Peter; Zaccarelli, Emanuela; Stradner, Anna.

I: Molecular Pharmaceutics, Bind 16, Nr. 6, 2019, s. 2394-2404.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

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

PY - 2019

Y1 - 2019

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 - Self-assembly

KW - Patchy colloids

KW - Antibodies

KW - Self-assembly

KW - Patchy colloids

U2 - 10.1021/acs.molpharmaceut.9b00019

DO - 10.1021/acs.molpharmaceut.9b00019

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JO - Molecular Pharmaceutics

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Skar-Gislinge N, Ronti M, Garting T, Rischel C, Schurtenberger P, Zaccarelli E et al. A Colloid Approach to Self-Assembling Antibodies. Molecular Pharmaceutics. 2019;16(6):2394-2404. https://doi.org/10.1021/acs.molpharmaceut.9b00019