Adsorption of a cationic amphiphilic drug on human serum albumin: characterization of the complex

The complex formed by the interaction of the amphiphilic drug verapamil hyd rochloride and human serum albumin (HSA) in water at 25 degreesC was invest igated using a range of physico-chemical techniques. The colloidal dispersi on was considered as a binary system in which water and verapamil molecules are regarded as the solvent for the HSA-verapamil complex. Measurements of the solution conductivity and the electrophoretic mobility of the complexe s showed an ionic adsorption of the drug on the protein surface leading to surface saturation at a verapamil concentration between 10 and 15 mmol kg(- 1). Measurements of the size of the complex and the thickness of the adsorb ed layer by dynamic light scattering showed a gradual change in hydrodynami c radius of the complex with increasing drug concentration typical of a sat uration rather than a denaturation process, the magnitude of the change bei ng insufficient to account for any appreciable extension or unfolding of th e HSA molecule. The interaction potential between the HSA-verapamil complex es and their stability were determined from the dependence of the diffusion coefficients on protein concentration by application of the DLVO colloidal stability theory. The results indicate decreasing stability of the colloid al dispersion of the drug-protein complexes with increase in the concentrat ion of added drug.