L.M. Lacava

Magnetic Resonance of a Dextran-Coated Magnetic Fluid Intravenously Administered in Mice

Magnetic resonance was used to investigate the kinetic disposition of magnetite nanoparticles (9.4 nm core diameter) from the blood circulation after intravenous injection of magnetite-based dextran-coated magnetic fluid in female Swiss mice. In the first 60 min the time-decay of the nanoparticle concentration in the blood circulation follows the one-exponential (one-compartment) model with a half-life of (6.9 +/- 0.7) min. The X-band spectra show a broad single line at g approximately 2, typical of nanomagnetic particles suspended in a nonmagnetic matrix. The resonance field shifts toward higher values as the particle concentration reduces, following two distinct regimes. At the higher concentration regime (above 10(14) cm(-3)) the particle-particle interaction responds for the nonlinear behavior, while at the lower concentration regime (below 10(14) cm(-3)) the particle-particle interaction is ruled out and the system recovers the linearity due to the demagnetizing field effect alone.

Biological effects of magnetic fluids: toxicity studies

Toxicity of ionic and citrate-based magnetic fluids administrated intraperitoneally to mice was investigated through cytogenetic analysis, evaluation of mitotic index and morphological and cytometric alterations. Both magnetic fluid samples cause severe inflammatory reactions, being very toxic and thus not biocompatible. Peritoneal cells and tissues studies may provide a useful strategy to investigate the in vivo biological effects of magnetic nanoparticles.

Toxic effects of ionic magnetic fluids in mice

Abstract Toxicity of ionic and tartrate-based magnetic fluids administered intraperitoneally to mice was investigated through morphological and cytometric alterations and cytogenetic analysis. Both magnetic fluids cause cellular death, mutagenicity and severe inflammatory reactions, being very toxic and thus not biocompatible. Peritoneal cell and tissue studies may provide a useful strategy to investigate the in vivo biological effects of magnetic nanoparticles.

The influence of aggregates and relative permeability on the magnetic birefringence in ionic magnetic fluids

The static magnetic birefringence (SMB) of nickel-ferrite ionic magnetic fluid was investigated within the oscillating dipole-interaction anisotropy concept proposed by Xu and Ridler [J. Appl. Phys. 82, 326 (1997)]. The model was extended to include the magnetic texture of particle agglomerates and the field dependence of the magnetic permeability. The SMB data of samples subjected or not to a magnetic aging process and presenting particle concentration in the range of 2×1016 to 8×1016 particle/cm3 were successfully described. The particle size distribution obtained from the fit of the SMB data was discussed in comparison with the data obtained from transmission electron microscopy.

Light microscopy and magnetic resonance characterization of a DMSA-coated magnetic fluid in mice

Light microscopy and magnetic resonance were used to investigate the biodistribution of magnetite nanoparticles coated with dimercaptosuccinic acid, after intravenous injection of a single dose in mice. Morphological analysis showed a huge amount of magnetic nanoparticles (MNPs) in the lung 30 min after injection. In contrast to the lung, morphological analysis revealed lower concentration of MNPs in the liver. A progressive decrease of MNPs in both lung and liver was observed from 30 min to 4 hours after intravenous injection. MNPs were not observed in any other organs using morphological analysis. In support of the LM observations MR signals were detected in both lung and liver as early as 5 min after injection. In addition, no MR signal was observed in the blood stream as early as 5 min after injection of the single dose.

Nanoparticle sizing: a comparative study using atomic force microscopy, transmission electron microscopy, and ferromagnetic resonance

Abstract Atomic force microscopy (AFM), transmission electron microscopy (TEM), and ferromagnetic resonance (FMR) were used to unfold the nanoparticle size of a ferrofluid sample. Compared to TEM, the AFM method showed a nanoparticle diameter (Dm) reduction of 20% and standard deviation (σ) increase of 15%. The differences in Dm and σ were associated with the AFM tip and the nanoparticle concentration on the substrate.

A double-coated magnetite-based magnetic fluid evaluation by cytometry and genetic tests

Abstract Magnetite nanoparticles pre-coated with dodecanoic acid and ethoxylated alcohol (DE) were used to obtain a physiologically stable magnetic fluid (DE–MF) sample. Three different doses of DE–MF were intraperitoneally applied to mice. Blood and peritoneum cytometry and micronucleus test were performed for 1–21 days after injection to investigate the DE–MF toxicity. Changes in cell population, peritoneum inflammation, and potential DE–MF genotoxic action were all time and dose dependent. At the lowest dose (5×1015 particles/kg), DE–MF seems to be useful as a drug precursor with both diagnostic and therapeutic values.

Biological investigation of a citrate-coated cobalt-ferrite-based magnetic fluid

The present study reports on several in vivo biological tests carried out with a cobalt–ferrite, citrate-coated, magnetic fluid sample developed for biomedical purposes. Systematic biological investigation was performed after endovenous injection in mice. Morphological analysis showed magnetic nanoparticle (MNP) infiltration in the parenchyma or vessels of all investigated organs. Nevertheless, at the investigated dose and period of treatment, no cell damage or inflammatory processes were observed. Cytometry alterations and genotoxic effects were not observed. Although precipitation of MNPs in tissues may be taken as undesirable, the absence of morphological alterations is very promising. The data show that the investigated sample is biocompatible and useful for biomedical applications.

Magnetic resonance and light microscopy investigation of a dextran coated magnetic fluid

A dextran-coated magnetite-based magnetic fluid (MF) sample (DexMF) was developed for cancer diagnostic and therapeutic purposes. In order to perform biological studies DexMF samples were endovenously injected into female Swiss mice. Magnetic resonance (MR) spectra showed a broad line around g=2, typical of magnetic nanoparticles (MNPs) suspended in a nonmagnetic matrix. The MR data showed that MNPs essentially spread in liver, spleen, and bone marrow. MNPs in blood stream were found up to 60 min after injection. Histological analysis also showed MNP agglomeration in liver, spleen, and bone marrow, from 1 h up to 28 days. No damaged cells or any other kind of alteration were observed in the investigated tissues. The data suggested that DexMF sample is biocompatible and adequate for biomedical applications.

Biodistribution and biocompatibility investigation in magnetoliposome treated mice

Magnetoliposomes (MLs) may be successfully applied for several purposes. A dimyristoylphosphatidyl-choline- based ML (ML-2) sample was developed as a precursor of more complex thermal cancer therapy systems. The present study reports on morphology and magnetic resonance (MR) investigations carried out with the magnetite-based ML-2 sample. For the experiments, adult female Swiss mice were endovenously treated with a bolus dose of 100 µl of ML-2. Morphology and room-temperature MR studies (X-band experiments) were performed in several organs collected from 1 hour to 28 days after ML administration. Histological data showed magnetic nanoparticle (MNP) clusters up to the 28th day in the liver and spleen tissues. In spite of the presence of MNP clusters, no morphological alterations were observed, supporting the biocompatibility of the ML-2. MR signal was detected only in the liver and spleen tissues and showed that the MNPs concentration was not altered from 48 hours to 28 days after ML injection. Using MR data, important pharmacokinetic parameters, such as the effective clearance (half-life) and peak concentration, were obtained for the liver and spleen.