Looking at the albumin-drug binding via partitioning in aqueous two-phase system

• Published in: Biochemical and biophysical research communications 2025-01, Vol.745, p.151245, Article 151245
• Main Authors: Madeira, Pedro P., Uversky, Vladimir N., Zaslavsky, Boris Y.
• Format: Article
• Language: English
• ISSN: 0006-291X; 1090-2104; 1090-2104
• DOI: 10.1016/j.bbrc.2024.151245

The partition coefficient of human serum albumin (HSA) was analyzed in the PEG600-Dex70, 0.15 M NaCl/KCl in 0.01 M Na/K phosphate buffer, pH 7.4 aqueous two-phase system, with varying concentrations of ten different drugs: caffeine, cefmetazole, oxacillin, propranolol, theophylline, verapamil, warfarin, atenolol, diltiazem, and terbutaline. All the drugs were found to increase HSA's partition coefficient, but they affected its behavior differently. We empirically determined that an exponential equation could describe the dependence of the partition coefficient for each drug. Notably, we observed a correlation between the drug's clearance times in the human body and the parameters of the exponential equation. This suggests a link between the efficiency of drug clearance from the bloodstream and the conformational changes in HSA, induced by its interaction with the drug, and the characteristics of partitioning the resulting HSA-drug complex in the aqueous two-phase system. •Partitioning of HSA in aqueous two-phase system changes under interaction with drugs.•The drug-induced changes are drug structure and concentration-dependent.•All ten drugs examined change the albumin conformation.•Partition behavior of HAS-drug complex correlates with the drug clearance time.