Interfacial dilatational deformation accelerates particle formation in monoclonal antibody solutions

Soft Matter
Gigi L LinGerald G Fuller

Abstract

Protein molecules are amphiphilic moieties that spontaneously adsorb at the air/solution (A/S) interface to lower the surface energy. Previous studies have shown that hydrodynamic disruptions to these A/S interfaces can result in the formation of protein aggregates that are of concern to the pharmaceutical industry. Interfacial hydrodynamic stresses encountered by protein therapeutic solutions under typical manufacturing, filling, and shipping conditions will impact protein stability, prompting a need to characterize the contribution of basic fluid kinematics to monoclonal antibody (mAb) destabilization. We demonstrate that dilatational surface deformations are more important to antibody stability when compared to constant-area shear of the A/S interface. We have constructed a dilatational interfacial rheometer that utilizes simultaneous pressure and bubble shape measurements to study the mechanical stability of mAbs under interfacial aging. It has a distinct advantage over methods utilizing the Young-Laplace equation, which incorrectly describes viscoelastic interfaces. We provide visual evidence of particle ejection from dilatated A/S interfaces and spectroscopic data of ejected mAb particles. These rheological studies frame ...Continue Reading

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Citations

Sep 20, 2016·Langmuir : the ACS Journal of Surfaces and Colloids·Danielle L LeiskeMartha Lovato Tse
Nov 1, 2016·Langmuir : the ACS Journal of Surfaces and Colloids·V Chandran SujaG G Fuller
May 1, 2017·Journal of Pharmaceutical Sciences·Christine ProbstRong-Rong Zhu
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Dec 28, 2017·Proceedings of the National Academy of Sciences of the United States of America·Amit Kumar Sachan, Joseph A Zasadzinski
May 2, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Peter HollowellJian R Lu
Nov 9, 2020·Advances in Colloid and Interface Science·V Chandran SujaG G Fuller
Dec 4, 2020·Journal of Pharmaceutical Sciences·Caitlin V WoodChristopher J Roberts
Jan 14, 2020·Journal of Pharmaceutical Sciences·Caitlin V WoodChristopher J Roberts
Feb 24, 2021·Pharmaceutical Research·Yuchen ZhangArezoo M Ardekani
Dec 19, 2017·Langmuir : the ACS Journal of Surfaces and Colloids·Aadithya KannanGerald G Fuller
Jan 10, 2020·Molecular Pharmaceutics·Marie R G KoppPaolo Arosio
Aug 29, 2021·Science Advances·Ankit KantheRaymond S Tu
Sep 11, 2021·International Journal of Pharmaceutics·Yuchen ZhangArezoo M Ardekani

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