Chemical modifications of Superparamagnetic Iron Oxide Nanoparticles (SPION) surfaces by attachment of functional groups and further covalent coupling with biodegradable substances have been studied. Based on computer-assisted chemical equilibrium calculations, several optimum operation conditions for a coprecipitation process of magnetite nanoparticles were predicted. These particles were immobilized by ultra-thin films of PVA, Dextran, Dextrin, PEG and MPEG to obtain a biocompatible particle surface for further functionalization purposes. The effect of surface modification of the superparamagnetic nanoparticles in terms of chemical and physical properties of the samples was investigated with several techniques, including microelectrophoresis measurement. The feasibility of using SPION in biomedical applications was investigated by in-vivo treatment in rat brains.