Influence of low molecular weight salts on the viscosity of aqueous-buffer bovine serum albumin solutions

Blaž Zdovc (Author), Matej Jaklin (Author), Barbara Hribar (Author), Miha Lukšič (Author)

Abstract

Pharmaceutical design of protein formulations aims at maximum efficiency (protein concentration) and minimum viscosity. Therefore, it is important to know the nature of protein-protein interactions and their influence on viscosity. In this work, we investigated the dependence of the viscosity of BSA in an aqueous 20 mM acetate buffer at pH = 4.3 on protein concentration and on temperature (5–45 °C). The viscosity of the solution increased with protein concentration and was 230% higher than the viscosity of the protein-free formulation at 160 mg/mL. The viscosity decreased by almost 60% in the temperature range from 5 to 45 °C. The agreement of the modified Arrhenius theory with experiment was quantitative, whereas a hard-sphere model provided only a qualitative description of the experimental results. We also investigated the viscosity of a 100 mg/mL BSA solution as a function of the concentration of added low molecular weight salts (LiCl, NaCl, KCl, RbCl, CsCl, NaBr, NaI) in the range of salt concentrations up to 1.75 mol/L. In addition, the particle size and zeta potential of BSA-salt mixtures were determined for solutions containing 0.5 mol/L salt. The trends with respect to the different anions followed a direct Hofmeister series (Cl$^–$ > Br$^–$ > I$^–$), whereas for cations in the case of viscosity the indirect Hofmeister series was observed (Li$^+$ > Na$^+$ > K$^+$ > Rb$^+$ > Cs$^+$), but the values of particle sizes and zeta potential did not show cation-specific effects. Since the protein is positively charged at pH = 4.3, anions are more attracted to the protein surface and shield its charge, while the interaction with cations is less pronounced. We hypothesize that salt surface charge shielding reduces protein colloidal stability and promotes protein aggregate formation.

Keywords

proteini;goveji serumski albumin;soli;viskoznost;zeta potencial;

Data

Language:	English
Year of publishing:	2022
Typology:	1.01 - Original Scientific Article
Organization:	UL FKKT - Faculty of Chemistry and Chemical Technology
UDC:	577.322
COBISS:	96153859
ISSN:	1420-3049
Views:	97
Downloads:	39
Average score:	0 (0 votes)
Metadata:

Other data

Secondary language:	Slovenian
Secondary keywords:	proteini;goveji serumski albumin;soli;viskoznost;zeta potencial;
Type (COBISS):	Article
Pages:	str. 1-16
Volume:	ǂVol. ǂ27
Issue:	ǂiss. ǂ3
Chronology:	Feb. 2022
DOI:	10.3390/molecules27030999
ID:	15437264