A Study of the Interaction of the Amphiphilic Penicillins Cloxacillin and Dicloxacillin with Human Serum Albumin in Aqueous Solution

Abstract

The complex formed by the interaction of the structurally similar amphiphilic penicillin drugs cloxacillin and dicloxacillin and human serum albumin (HSA) in water at 25 °C has been investigated using a range of physicochemical techniques. The colloidal dispersion has been considered as a binary system in which water and drug molecules are regarded as the solvent for the HSA/drug complex. Measurements of the solution conductivity and the electrophoretic mobility of the complexes have shown hydrophobic adsorption of the drug on the protein surface, leading to surface saturation. Measurements of the size of the complex and the thickness of the adsorbed layer by dynamic light scattering have shown a gradual increase in hydrodynamic radius of the complex with increasing drug concentration typical of a saturation rather than a denaturation process. A larger hydrodynamic radius of the HSA/dicloxacillin complex has been attributed to a more pronounced extension or unfolding of the HSA molecule than in complexes formed with cloxacillin. The interaction potential between the HSA/drug complexes and their stability were determined from the dependence of diffusion coefficients on protein concentration by application of the DLVO colloidal stability theory. The results indicate decreasing stability of the colloidal dispersion of the protein/drug complexes with increase in the concentration of added drug.