NDLI: Viscosity Analysis of Dual Variable Domain Immunoglobulin Protein Solutions: Role of Size, Electroviscous Effect and Protein-Protein Interactions

Content Provider	Springer Nature Link
Author	Raut, Ashlesha S. Kalonia, Devendra S.
Copyright Year	2015
Abstract	Increased solution viscosity results in difficulties in manufacturing and delivery of therapeutic protein formulations, increasing both the time and production costs, and leading to patient inconvenience. The solution viscosity is affected by the molecular properties of both the solute and the solvent. The purpose of this work was to investigate the effect of size, charge and protein-protein interactions on the viscosity of Dual Variable Domain Immunoglobulin (DVD-Ig$^{TM}$) protein solutions.The effect of size of the protein molecule on solution viscosity was investigated by measuring intrinsic viscosity and excluded volume calculations for monoclonal antibody (mAb) and DVD-Ig$^{TM}$ protein solutions. The role of the electrostatic charge resulting in electroviscous effects for DVD-Ig$^{TM}$ protein was assessed by measuring zeta potential. Light scattering measurements were performed to detect protein-protein interactions affecting solution viscosity.DVD-Ig$^{TM}$ protein exhibited significantly higher viscosity compared to mAb. Intrinsic viscosity and excluded volume calculations indicated that the size of the molecule affects viscosity significantly at higher concentrations, while the effect was minimal at intermediate concentrations. Electroviscous contribution to the viscosity of DVD-Ig$^{TM}$ protein varied depending on the presence or absence of ions in the solution. In buffered solutions, negative k $_{ D }$ and B $_{ 2 }$ values indicated the presence of attractive interactions which resulted in high viscosity for DVD-Ig$^{TM}$ protein at certain pH and ionic strength conditions.Results show that more than one factor contributes to the increased viscosity of DVD-Ig$^{TM}$ protein and interplay of these factors modulates the overall viscosity behavior of the solution, especially at higher concentrations.
Starting Page	155
Ending Page	166
Page Count	12
File Format	PDF
ISSN	07248741
Journal	Pharmaceutical Research
Volume Number	33
Issue Number	1
e-ISSN	1573904X
Language	English
Publisher	Springer US
Publisher Date	2015-08-19
Publisher Place	New York
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Pharmacology/Toxicology Pharmacy Biochemistry Medical Law Biomedical Engineering
Content Type	Text
Resource Type	Article
Subject	Organic Chemistry Pharmacology Molecular Medicine Pharmacology (medical) Biotechnology Pharmaceutical Science

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