caa a22 4500 445313706 CHVBK 20180317142639.0 cr unu---uuuuu 170323e20110801xx s 000 0 eng 10.1007/s11095-011-0424-7 doi (NATIONALLICENCE)springer-10.1007/s11095-011-0424-7 Viscosity Analysis of High Concentration Bovine Serum Albumin Aqueous Solutions [Elektronische Daten] [Sandeep Yadav, Steven Shire, Devendra Kalonia] ABSTRACT: Purpose: To understand the apparent inconsistency between the dilute and high concentration viscosity behavior of bovine serum albumin (BSA). Method: Zeta potential and molecular charge on BSA were determined from Electrophoretic mobility measurements. Second virial coefficient (B 22) and interaction parameter (k D) obtained from static and dynamic light scattering, respectively, quantified intermolecular interactions. Rheology studies characterized viscoelasticity at high concentration. The dipole moment was calculated using Takashima's approximation for proton fluctuations over charged residues. Results: The effective isoelectric point of BSA was pH 4.95. In dilute solutions (≤ 40mg/ml), the viscosity was minimal at the pI; at high concentrations, pH 5.0 solutions were most viscous. B 22 and k D showed intermolecular attractions at pH 5.0; repulsions dominated at other pHs. The attractive interactions led to a high storage modulus (G′) at pH 5.0. Conclusion: In dilute solutions, the electroviscous effect due to net charge governs the viscosity behavior; at high concentrations, the solution viscosity cannot be justified based on a single parameter. The net interplay of all intermolecular forces dictates viscosity behavior, wherein intermolecular attraction leads to a higher solution viscosity. Springer Science+Business Media, LLC, 2011 dipole moment nationallicence high concentration viscosity nationallicence interaction parameter ( k D) nationallicence intermolecular interaction nationallicence protein charge nationallicence second virial coefficient ( B 22) nationallicence zeta potential nationallicence Yadav Sandeep Department of Pharmaceutical Sciences, University of Connecticut, 06269, Storrs, CT, USA aut Shire Steven Late Stage Pharmaceutical Development, Genentech, Inc., 1 DNA Way, 94080, South San Francisco, CA, USA aut Kalonia Devendra Department of Pharmaceutical Sciences, University of Connecticut, 06269, Storrs, CT, USA aut Pharmaceutical Research Springer US; http://www.springer-ny.com 28/8(2011-08-01), 1973-1983 0724-8741 28:8<1973 2011 28 11095 https://doi.org/10.1007/s11095-011-0424-7 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s11095-011-0424-7 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Yadav Sandeep Department of Pharmaceutical Sciences, University of Connecticut, 06269, Storrs, CT, USA aut NATIONALLICENCE 700 1- Shire Steven Late Stage Pharmaceutical Development, Genentech, Inc., 1 DNA Way, 94080, South San Francisco, CA, USA aut NATIONALLICENCE 700 1- Kalonia Devendra Department of Pharmaceutical Sciences, University of Connecticut, 06269, Storrs, CT, USA aut NATIONALLICENCE 773 0- Pharmaceutical Research Springer US; http://www.springer-ny.com 28/8(2011-08-01), 1973-1983 0724-8741 28:8<1973 2011 28 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer