The interaction between the drug donepezil and human serum albumin (HSA) was examined on the surface of amine modified superparamagnetic iron oxide nanoparticles (SPIONs), which were synthesized by the coprecipitation of ferrous and ferric salts with NH4OH and then modified with [3-Aminopropyl] triethoxysilane (APTES) to obtain functional amine groups on the nanoparticles' surface. Albumin's binding capacity to APTES-modified SPIONs was estimated by fluorescence spectroscopy. After HSA was bound to the APTES modified SPIONs, donepezil was interacted with the HSA-SPIONs. The binding capacity of the drug was determined using a calibration curve equation that was drawn using fluorescence spectroscopy at 325 and 387nm, the excitation and emission wavelengths. Thermodynamic parameters were estimated for the interaction of HSA and donepezil on amine-modified SPIONs. Binding was carried out spontaneously via electrostatic interaction. Binding was also examined by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), scanning electron microscopy (SEM) and zeta-potential measurements. © 2013 Elsevier B.V.