Development and Evaluation of the Magnetic Properties of a New Manganese (II) Complex: A Potential MRI Contrast Agent.

Magnetic resonance imaging (MRI) is a non-invasive powerful modern clinical technique that is extensively used for the high-resolution imaging of soft tissues. To obtain high-definition pictures of tissues or of the whole organism this technique is enhanced by the use of contrast agents. Gadolinium-based contrast agents have an excellent safety profile. However, over the last two decades, some specific concerns have surfaced. Mn(II) has different favorable physicochemical characteristics and a good toxicity profile, which makes it a good alternative to the Gd(III)-based MRI contrast agents currently used in clinics. Mn(II)-disubstituted symmetrical complexes containing dithiocarbamates ligands were prepared under a nitrogen atmosphere. The magnetic measurements on Mn complexes were carried out with MRI phantom measurements at 1.5 T with a clinical magnetic resonance. Relaxivity values, contrast, and stability were evaluated by appropriate sequences. Studies conducted to evaluate the properties of paramagnetic imaging in water using a clinical magnetic resonance showed that the contrast, produced by the complex [Mn(II)(L')2] × 2H2O (L' = 1.4-dioxa-8-azaspiro[4.5]decane-8-carbodithioate), is comparable to that produced by gadolinium complexes currently used in medicine as a paramagnetic contrast agent.

Synthetic and Nanotechnological Approaches for a Diagnostic Use of Manganese.

The development of multimodal imaging techniques such as positron emission tomography (PET) and magnetic resonance imaging (MRI) allows the contemporary obtaining of metabolic and morphological information. To fully exploit the complementarity of the two imaging modalities, the design of probes displaying radioactive and magnetic properties at the same time could be very beneficial. In this regard, transition metals offer appealing options, with manganese representing an ideal candidate. As nanosized imaging probes have demonstrated great value for designing advanced diagnostic/theranostic procedures, this work focuses on the potential of liposomal formulations loaded with a new synthesized paramagnetic Mn(II) chelates. Negatively charged liposomes were produced by thin-layer hydration method and extrusion. The obtained formulations were characterized in terms of size, surface charge, efficiency of encapsulation, stability over time, relaxivity, effective magnetic moment, and in vitro antiproliferative effect on human cells by means of the MTT assay. The negatively charged paramagnetic liposomes were monodisperse, with an average hydrodynamic diameter not exceeding 200 nm, and they displayed good stability and no cytotoxicity. As determined by optical emission spectroscopy, manganese complexes are loaded almost completely on liposomes maintaining their paramagnetic properties.

Thermal Magnetic Field Activated Propolis Release From Liquid Crystalline System Based on Magnetic Nanoparticles.

Intra-periodontal pocket drug delivery systems, such as liquid crystalline systems, are widely utilized improving the drug release control and the therapy. Propolis is used in the treatment of periodontal diseases, reducing the inflammatory and infectious conditions. Iron oxide magnetic nanoparticles (MNPs) can improve the treatment when an alternating external magnetic field (AEMF) is applied, increasing the local temperature. The aim of this study was to develop a liquid crystalline system containing MNPs for intra-periodontal pocket propolis release. MNPs were prepared using iron salts and the morphological, size, thermal, x-ray diffraction, magnetometry, and Mössbauer spectroscopy analyses were performed. Cytotoxicity studies using Artemia salina and fibroblasts were also accomplished. The systems were prepared using polyoxyethylene (10) oleyl ether, isopropyl myristate, purified water, and characterized by polarized optical microscopy, rheometry, and in vitro drug release profile using a periodontal pocket simulator apparatus. The antifungal activity of the systems was investigated against Candida spp. using an AEMF. MNPs displayed nanometric size, were monodisperse, and they displayed very low cytotoxicity. Microscopically homogeneous formulations were obtained displaying important physicochemical and biological properties. The system displayed prolonged release of propolis and important in vitro fungicide activity, which was increased when the AEMF was applied, indicating a potentially alternative therapy for the treatment of the periodontal disease.

Silk fibroin films with embedded magnetic nanoparticles: evaluation of the magneto-mechanical stimulation effect on osteogenic differentiation of stem cells.

We report about a biomaterial in the form of film ∼10 µm thick, consisting of a silk fibroin matrix with embedded iron oxide superparamagnetic nanoparticles, for prospective applications as bioactive coating in regenerative medicine. Films with different load of magnetic nanoparticles are produced (nanoparticles/silk fibroin nominal ratio = 5, 0.5 and 0 wt%) and the structural, mechanical and magnetic properties are studied. The nanoparticles form aggregates in the silk fibroin matrix and the film stiffness, as tested by nanoindentation, is spatially inhomogeneous, but the protein structure is not altered. In vitro biological tests are carried out on human bone marrow-derived mesenchymal stem cells cultured on the films up to 21 days, with and without an applied static uniform magnetic field. The sample with the highest nanoparticles/silk fibroin ratio shows the best performance in terms of cell proliferation and adhesion. Moreover, it promotes a faster and better osteogenic differentiation, particularly under magnetic field, as indicated by the gene expression level of typical osteogenic markers. These findings are explained in light of the results of the physical characterization, combined with numerical calculations. It is established that the applied magnetic field triggers a virtuous magneto-mechanical mechanism in which dipolar magnetic forces between the nanoparticle aggregates give rise to a spatial distribution of mechanical stresses in the silk fibroin matrix. The film with the largest nanoparticle load, under cell culture conditions (i.e. in aqueous environment), undergoes matrix deformations large enough to be sensed by the seeded cells as mechanical stimuli favoring the osteogenic differentiation.

Effects of Microencapsulated Ferulic Acid or Its Prodrug Methyl Ferulate on Neuroinflammation Induced by Muramyl Dipeptide.

Ferulic acid (Fer) is known for its antioxidant and anti-inflammatory activities, which are possibly useful against neurodegenerative diseases. Despite the ability of Fer to permeate the brain, its fast elimination from the body does not allow its therapeutic use to be optimized. The present study proposes the preparation and characterization of tristearin- or stearic acid-based solid lipid microparticles (SLMs) as sustained delivery and targeting systems for Fer. The microparticles were produced by conventional hot emulsion techniques. The synthesis of the methyl ester of Fer (Fer-Me) allowed its encapsulation in the SLMs to increase. Fer-Me was hydrolyzed to Fer in rat whole blood and liver homogenate, evidencing its prodrug behavior. Furthermore, Fer-Me displayed antioxidant and anti-inflammatory properties. The amount of encapsulated Fer-Me was 0.719 ± 0.005% or 1.507 ± 0.014% in tristearin or stearic acid SLMs, respectively. The tristearin SLMs were able to control the prodrug release, while the stearic acid SLMs induced a significant increase of its dissolution rate in water. Jointly, the present results suggest that the tristearin SLMs loaded with Fer-Me could be a potential formulation against peripheral neuropathic pain; conversely, the stearic acid SLMs could be useful for Fer-Me uptake in the brain after nasal administration of the formulation.

Mixing iron oxide nanoparticles with different shape and size for tunable magneto-heating performance.

Tuning the magnetic properties of nanoparticles is a strategic goal to use them in the most effective way to perform specific functions in the nanomedicine field. We report a systematic study carried out on a set of samples obtained by mixing together iron oxide nanoparticles with different shape: elongated with aspect ratio ∼5.2 and mean volume of the order of 103 nm3 (excluding the silica coating) and spherical with mean volume one order of magnitude larger. These structural features of the nanoparticles together with their aggregation state determine the magnetic anisotropy and the magnetic relaxation processes. In particular, the spherical nanoparticles turn out to be more stable against superparamagnetic relaxation. Mixing the nanoparticles in different proportions allows to modulate the magnetic response of the samples. The two populations of nanoparticles magnetically influence each other through a mean field mechanism, which depends crucially on temperature and rules the hysteretic magnetic properties and their thermal evolution. This magnetic phenomenology has a direct impact on the ability of the mixed samples to generate heat under an alternating magnetic field, a key function in view of nanomedicine applications. Under proper testing conditions, the heating efficiency of the mixed samples is larger compared to that obtained as the sum of those of the parent nanoparticles. This occurs thanks to the mean field produced by the magnetically blocked spherical nanoparticles that stabilizes the thermally fluctuating moments of the elongated ones, which therefore contribute more effectively to the heat production.

Nanoparticles for Magnetic Heating: When Two (or More) Is Better Than One.

The increasing use of magnetic nanoparticles as heating agents in biomedicine is driven by their proven utility in hyperthermia therapeutic treatments and heat-triggered drug delivery methods. The growing demand of efficient and versatile nanoheaters has prompted the creation of novel types of magnetic nanoparticle systems exploiting the magnetic interaction (exchange or dipolar in nature) between two or more constituent magnetic elements (magnetic phases, primary nanoparticles) to enhance and tune the heating power. This process occurred in parallel with the progress in the methods for the chemical synthesis of nanostructures and in the comprehension of magnetic phenomena at the nanoscale. Therefore, complex magnetic architectures have been realized that we classify as: (a) core/shell nanoparticles; (b) multicore nanoparticles; (c) linear aggregates; (d) hybrid systems; (e) mixed nanoparticle systems. After a general introduction to the magnetic heating phenomenology, we illustrate the different classes of nanoparticle systems and the strategic novelty they represent. We review some of the research works that have significantly contributed to clarify the relationship between the compositional and structural properties, as determined by the synthetic process, the magnetic properties and the heating mechanism.

Novel Magnetic Inorganic Composites: Synthesis and Characterization.

The addition of magnetic particles to inorganic matrices can produce new composites exhibiting intriguing properties for practical applications. It has been previously reported that the addition of magnetite to concrete improves its mechanical properties and durability in terms of water and chloride ions absorption. Here we describe the preparation of novel magnetic geopolymers based on two different matrices (G1 without inert aggregates and G2 with inert quartz aggregates) containing commercial SrFe12O19 particles with two weight concentrations, 6% and 11%. The composites' characterization, including chemical, structural, morphological, and mechanical determinations together with magnetic and electrical measurements, was carried out. The magnetic study revealed that, on average, the SrFe12O19 magnetic particles can be relatively well dispersed in the inorganic matrix. A substantial increase in the composite samples' remanent magnetization was obtained by embedding in the geopolymer SrFe12O19 anisotropic particles at a high concentration under the action of an external magnetic field during the solidification process. The new composites exhibit good mechanical properties (as compressive strength), higher than those reported for high weight concretes bearing a similar content of magnetite. The impedance measurements indicate that the electrical resistance is mainly controlled by the matrix's chemical composition and can be used to evaluate the geopolymerization degree.

Synthesis of Ferrofluids Made of Iron Oxide Nanoflowers: Interplay between Carrier Fluid and Magnetic Properties.

Ferrofluids are nanomaterials consisting of magnetic nanoparticles that are dispersed in a carrier fluid. Their physical properties, and hence their field of application are determined by intertwined compositional, structural, and magnetic characteristics, including interparticle magnetic interactions. Magnetic nanoparticles were prepared by thermal decomposition of iron(III) chloride hexahydrate (FeCl3·6H2O) in 2-pyrrolidone, and were then dispersed in two different fluids, water and polyethylene glycol 400 (PEG). A number of experimental techniques (especially, transmission electron microscopy, Mössbauer spectroscopy and superconducting quantum interference device (SQUID) magnetometry) were employed to study both the as-prepared nanoparticles and the ferrofluids. We show that, with the adopted synthesis parameters of temperature and FeCl3 relative concentration, nanoparticles are obtained that mainly consist of maghemite and present a high degree of structural disorder and strong spin canting, resulting in a low saturation magnetization (~45 emu/g). A remarkable feature is that the nanoparticles, ultimately due to the presence of 2-pyrrolidone at their surface, are arranged in nanoflower-shape structures, which are substantially stable in water and tend to disaggregate in PEG. The different arrangement of the nanoparticles in the two fluids implies a different strength of dipolar magnetic interactions, as revealed by the analysis of their magnetothermal behavior. The comparison between the magnetic heating capacities of the two ferrofluids demonstrates the possibility of tailoring the performances of the produced nanoparticles by exploiting the interplay with the carrier fluid.