DEVELOPMENT OF SUPERPARAMAGNETIC NANOPARTICLES FOR MRI - EFFECT OF PARTICLE-SIZE, CHARGE AND SURFACE NATURE ON BIODISTRIBUTION

Twelve superparamagnetic Magnetite-Dextran (MD) nanoparticles potentia lly useful as contrast agents for Magnetic Resonance Imaging (MRI), wi th different sizes, charges and surface natures, were produced and int ernally labelled with Fe-59 in order to investigate the effect of thei r physicochemical properties on their biodistribution in mice. In a fi rst step, neutral MD particles of a size 33-90.6 nm were studied. Next , the influence of charge was investigated with negative and positive particles (MDL, MDD, MDDEAE). The former (-25, -30 mV) were small, aro und 30 nm in size whereas the latter (+20 mV) were larger (104 nm). Th e effect of surface nature was evaluated using MD particles coated wit h polyoxyethylene-polyoxypropylene copolymers (Synperonic(R)): these M DP particles were neutral and larger in size (65.9-76.4 nm). Experimen ts showed that 20 min post-injection (2 mg Fe/kg), liver uptake was en hanced when the mean diameter increased: 22% for the smallest and 42% for the largest. It was up to 3 x lower for electrically neutral parti cles than for charged particles. Coated particles presented higher vas cular persistence. The diagnostic potential for liver, lymph node or v ascular imaging were discussed.