Iron oxide nanoparticles synthesis optimized by design of experiments and magnetic particle imaging performance of magnetoliposomes

Iron oxide nanoparticles are clinically approved by Food and Drug Administration (FDA) in the United States of America, where are already used in cases of iron deficiency and as contrast agents for magnetic resonance imaging, highlighting the relevance of such nanomaterials in society. Liposomes are also accepted by FDA and the entrapment of iron oxide nanoparticles originates magnetoliposomes that represents one of the ways for combining magnetic nanoparticles and hydrophilic or hydrophobic molecules. Such combination can be useful for applications in combinatorial therapies, for instance, magnetic hyperthermia and Magnetic Particle Imaging (MPI), a new imaging modality. In this work, magnetic nanoparticles were synthesized by chemical coprecipitation, evaluating the effects of reactional parameters over the hydrodynamic diameter and composition of the samples by using Plackett-Burman experimental design. The results allowed a more reliable protocol, considering the experimental combinations that lead to smaller particles composed mostly of magnetite. Next, magnetoliposomes were prepared from magnetic nanoparticles stabilized by peptization. Characterization techniques were widely used and physical models were applied to data processing of magnetometry, magnetic susceptibility, and transmission electron microscopy. The magnetoliposomes performance as MPI tracers were compared to the nanoparticles (as-synthesized) and Ferucarbotran, the benchmark formulation. The results of this second stage of the work indicated improvement in the MPI physical signal per iron mass after the encapsulation, even though the most representative fraction of particles was governed by the Brownian relaxation mechanism. The magnetoliposomes had shown a signal more intense than Ferucarbotran, even with poorer resolution. This study can be useful for future works because one of the challenges in MPI researches is the production of tracers with performance equivalent to Ferucarbotran.