A Colloid Approach to Self-Assembling Antibodies
Version 3 2019-06-26, 13:35
Version 2 2019-06-20, 23:43
Version 1 2019-05-15, 17:45
Posted on 2019-06-26 - 13:35
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, Nicholas; Ronti, Michela; Garting, Tommy; Rischel, Christian; Schurtenberger, Peter; Zaccarelli, Emanuela; et al. (2019). A Colloid Approach to Self-Assembling Antibodies. ACS Publications. Collection. https://doi.org/10.1021/acs.molpharmaceut.9b00019
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AUTHORS (7)
NS
Nicholas Skar-Gislinge
MR
Michela Ronti
TG
Tommy Garting
CR
Christian Rischel
PS
Peter Schurtenberger
EZ
Emanuela Zaccarelli
AS
Anna Stradner
KEYWORDS
Colloid Approachchemical modificationsanisotropic shaperesults offerdiffusion coefficientmicrorheological experimentsmatter physics approachantibody formulationsshear viscositypatchy colloid modelpatchy modelreport resultscolloid-inspired approachSelf-Assembling Antibodies Concentrated solutionsproblemcharge distribution