Characterization of superparamagnetic iron oxide nanoparticles by asymmetrical flow-field-flow-fractionation

Aims: The further development of diagnostic and therapeutic nanomedicines in research and their translation into clinical practice require appropriate characterization methods to ensure a reproducible quality and performance. However, many methods are insufficient for a detailed analysis of the particle size. The primary aim of the present work is to evaluate the application of asymmetrical flow-field-flow-fractionation (AF4) coupled with multiangle laser and dynamic light scattering (DLS) for the characterization of superparamagnetic iron oxide (SPIO) particles. Methods: Eight carboxydextran-coated SPIO samples with different mean particle sizes, as determined by DLS, are investigated by means of an adequate AF4 separation method. Results: In this work, we show that, with increasing sample particle size, as measured by IDLS, the hydrodynamic and gyration radii obtained by the AF4 method increase respectively. We demonstrate that the applied AF4 method is able to separate nanoparticles of different sizes effectively, with superior reproducibility (relative standard deviation: < 3%) and high accuracy (relative standard deviation: < 10%). Furthermore, important characterization parameters that will affect the in vivo performance; namely, the shape factors and polydispersity indices, of all eight samples are presented. Conclusion: The work describes the application of AF4/DLS/multiangle laser light scattering as a highly useful method for characterization of SPIO particles, enabling valuable information to be accessed in addition to that obtained by transmission-electron microscopy and DLS in batch mode.