Excipients differentially influence the conformational stability and pretransition dynamics of two IgG1 monoclonal antibodies

Journal of Pharmaceutical Sciences
Santosh V ThakkarC Russell Middaugh

Abstract

Since immunoglobulins are conformationally dynamic molecules in solution, we studied the effect of stabilizing and destabilizing excipients on the conformational stability and dynamics of two IgG1 monoclonal antibodies (mAbs; mAb-A and mAb-B) using a variety of biophysical approaches. Even though the two mAbs are of the same IgG1 subtype, the unfolding patterns, aggregation behavior, and pretransition dynamics of these two antibodies were strikingly different in response to external perturbations such as pH, temperature, and presence of excipients. Sucrose and arginine were identified as stabilizers and destabilizers, respectively, on the basis of their influence on conformational stability for both the IgG1 mAbs. The two excipients, however, had distinct effective concentrations and different effects on the conformational stability and pretransition dynamics of the two mAbs as measured by a combination of differential scanning calorimetry, high-resolution ultrasonic spectroscopy, and red-edge excitation shift fluorescence studies. Stabilizing concentrations of sucrose were found to decrease the internal motions of mAb-B, whereas arginine marginally increased its adiabatic compressibility in the pretransition region. Both sucro...Continue Reading

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Citations

Oct 13, 2012·Journal of Pharmaceutical Sciences·Santosh V ThakkarC Russell Middaugh
Oct 2, 2012·Archives of Biochemistry and Biophysics·Christopher M Johnson
Jul 31, 2013·Protein Science : a Publication of the Protein Society·Santosh V ThakkarC Russell Middaugh
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Sep 15, 2021·Molecular Pharmaceutics·Harini NarayananPaolo Arosio

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