Adsorption of an amphiphilic penicillin onto human serum albumin: characterisation of the complex

The complex formed by the interaction of the amphiphilic penicillin drug na fcillin and human serum albumin (HSA) in water at 25 degreesC has been char acterised using a range of physicochemical techniques. Measurements of the solution conductivity and the electrophoretic mobility of the complexes hav e shown an ionic adsorption of the drug on the protein surface leading to a surface saturation at a nafcillin concentration of 0.012 mmol kg(-1) and s ubsequent formation of drug micelles in solutions of higher nafcillin conce ntration. Measurements of the size of the complex and the thickness of the adsorbed layer by static and dynamic light scattering have shown a gradual change in hydrodynamic radius of the complex with increasing drug concentra tion typical of a saturation rather than a denaturation process, the magnit ude of the change being insufficient to account for any appreciable extensi on or unfolding of the HSA molecule. The interaction potential between the HSA/nafcillin complexes, and the stability of the complexes were determined from the dependence of diffusion coefficients on protein concentration by application of the DLVO colloidal stability theory. The results indicate de creasing stability of the colloidal dispersion of the drug/protein complexe s with an increase in the concentration of added drug. (C) 2001 Elsevier Sc ience BY. All rights reserved.