Low-frequency Alternating Magnetic Field Research Articles

Original Empirical Research Protective Effects of Succinic Acid upon Exposure to the Low-Frequency Alternating Magnetic Field Determined in the Experiment

Introduction. The need to simulate the oxidative stress by an experiment of exposure to the low-frequency alternating magnetic field is induced by the persistent increase of the electromagnetic load on the endothermic organisms caused by the annual deterioration of the electromagnetic state of the environment. The low-frequency alternating magnetic field starts a chain of biochemical reactions in the laboratory animals, which alter the homeostasis against the increased intensity of free-radical oxidation (peroxidation) of biomembrane lipids. The preparations containing succinic acid have the antioxidant, antihypoxant, actoprotective and stress-protective effects, tested through various kind of modelling, however, the absence of data on the efficacy of succinic acid under the exposure to the alternating magnetic field has become the reason for the present experiment. The aim of the research is to determine the protective effects of succinic acid upon exposure of the laboratory rats to the low-frequency alternating magnetic field.Materials and Methods. The objects of the research were 90 white outbred male rats weighing 200–250 g, divided into three groups: group 1 — intact, the animals were in standard vivarium conditions and were not exposed to any effect; group 2 — control, the rats were exposed to the low frequency alternating magnetic field (LF-AMF) for 21 days daily per 3 hours, preceded by daily intraperitoneal administration to animals of the 0.9% sodium chloride solution at a dose of 1 ml / kg straight before them being exposed to LF-AMF; group 3 — experimental, the rats were daily intraperitoneally administered the succinic acid at a dose of 100 mg / kg (1 ml / kg) for 21 days prior to being exposed to LF-AMF. The exposure to the low-frequency alternating magnetic field was created by the Helmholtz coils (of diameter 1 m) powered by the alternating current source with a frequency of 50 Hz, with a magnetic field induction of 0.4 mT, whereas the cages with animals were placed in the centre of the device. The actoprotective effect of succinic acid was checked on the 7th, 14th and 21st days from the beginning of the experiment by duration of swimming of rats in water. The antioxidant effect — by concentration of diene conjugates, lipid hydroperoxides, malondialdehyde, ceruloplasmin, vitamin E in the blood plasma of rats measured according to the commonly accepted methods. The stress-protective effect was determined by the masses of the adrenal glands, thymus gland, spleen and the number of erosive defects on the suRussian Federationace of the gastric mucosa.Results. The experimental data has confirmed the actoprotective effect of succinic acid — the duration of swimming of the rats in the experimental group increased by 25–37% compared to the control one. The antioxidant effect of succinic acid under magnetic induction has been manifested in a decreased concentration of lipid peroxidation products against increased level of ceruloplasmin in the blood of rats in the experimental group compared to the animals in the control group. Administration of the succinic acid into the peritoneum of rats in the experimental group under exposure to the low frequency alternating magnetic field has prevented involution of the thymus gland by 45% (7th day), 56% (14th day), 71% (21th day) and the spleen by 52%, 58% and 66% respectively, alongside, the number of erosive and ulcerative defects on the suRussian Federationace of the gastric mucosa has decreased by 2.5–4 times compared to the animals in the control group.Discussion and Conclusion. The protective effects of succinic acid upon exposure to the low-frequency alternating magnetic field have been confirmed that include the stress-protective, actoprotective and antioxidant effects of the exogenous succinate. The ability of succinic acid to prevent the negative changes in the internal organs caused by the magnetic loads is proved by the statistically significant excess of the mass coefficients of the thymus gland and spleen in the experimental group, compared to the control one, along with the fewer erosive defects on the suRussian Federationace of the gastric mucosa. Succinic acid reduces the intensity of lipid peroxidation processes upon the magnetic exposure due to reducing the concentration of lipid peroxidation products and increasing the level of ceruloplasmin in the blood of animals.

Low frequency magnetic field assisted production of acidic protease by Aspergillus niger.

Acid protease is widely used in industries such as food processing and feed additives. In the study, low frequency magnetic field (LF-MF) as an aid enhances acid protease production by Aspergillus niger (A. niger). The study assessed mycelial biomass, the enzymic activity of the acidic protease and underlying mechanism. At low intensities, alternating magnetic field (AMF) is more effective than static magnetic fields (SMF). Under optimal magnetic field conditions, acid protease activity and biomass increased by 91.44% and 16.31%, as compared with the control, respectively. Maximum 19.87% increase in enzyme activity after magnetic field treatment of crude enzyme solution in control group. Transcriptomics analyses showed that low frequency alternating magnetic field (LF-AMF) treatment significantly upregulated genes related to hydrolases and cell growth. Our results showed that low-frequency magnetic fields can enhance the acid protease production ability of A. niger, and the effect of AMF is better at low intensities. The results revealed that the effect of magnetic field on the metabolic mechanism of A. niger and provided a reference for magnetic field-assisted fermentation of A. niger.

Magnetic iron oxide nanoparticles@lecithin/poly (l-lactic acid) microspheres for targeted drug release in cancer therapy

The use of targeted chemotherapy is a promising solution to mitigate the side effects and dosage of drugs. This research focuses on the development of magnetic microspheres (MMS) based drug carriers for targeted chemotherapy, formulated with iron oxide nanoparticles (Fe3O4 NPs) and poly (l-lactic acid) (PLA) loaded with the antibiotic drug Ciprofloxacin (CIF). In this study, Fe3O4 NPs were synthesized using pomegranate peel extract as a natural reducing and stabilizing agent. The double emulsification method (W1/O/W2) was employed to produce Fe3O4@LEC-CIF-PLA-MMS, which were characterized using various spectral and microscopic techniques. The drug encapsulation efficiency for Fe3O4@LEC-CIF-PLA-MMS was found to be 80.7 %. The in vitro drug release of CIF from Fe3O4@LEC-CIF-PLA-MMS induced by H2O2 and GSH- stimuli was found to be 87.55 % and 82.32 %, respectively in acidic pH 4.5. Notably, the magnetically triggered drug release behaviour of Fe3O4@LEC-CIF-PLA-MMS (93.56 %) was assessed in acidic pH environment upon exposure to low-frequency alternating magnetic field (LF-AMF). Fe3O4@LEC-CIF-PLA-MMS demonstrated significantly enhanced in vitro cytotoxicity (IC50 = 0.8 ± 0.03 μg/mL) against the HeLa-S3 cancer cell lines. Nevertheless, these research findings highlight the potential of Fe3O4@LEC-CIF-PLA-MMS for further development as a chemotherapeutic agent and hold promise for the future of targeted cancer treatment.

Effect of low-frequency alternating magnetic field on the rheological properties, water distribution and microstructure of low-salt pork batters

The effects of different intensities of low-frequency alternating magnetic fields (LF-AMF) modification on gel characteristics, rheology, water distribution, secondary structure and microstructure were investigated. The results showed that application of LF-AMF exhibited a significant improvement of the water-holding capacity, gel strength, color, textural properties and acceptability of low-salt pork batter gels (P < 0.05). When the LF-AMF intensity reached 0.6 mT, the low-salt pork batters had the highest WHC, L*, gel strength, hardness, springiness, gumminess and chewiness and acceptability (P < 0.05). During the temperature (sample heated from 20 to 80 °C) and frequency (0–10 Hz) sweep, the storage modulus G′ first increased and then decreased with increasing of LF-AMF intensity. Low-field nuclear magnetic resonance (LF-NMR) showed that LF-AMF at an intensity of 0.6 mT shortened the T2 relaxation time of pork batter gel and increased the proportion of immobilized water. Fourier transform infrared spectroscopy (FTIR) showed that LF-AMF treatment significantly induced an increase of β-sheet structure and reduction of α-helix content in pork batter gels (P < 0.05). Scanning electron microscopy (SEM) results suggested that LF-AMF contributed to the formation of pork batter gels with a more uniform and orderly network structure.

Encapsulation of gadolinium ferrite nanoparticle in generation 4.5 poly(amidoamine) dendrimer for cancer theranostics applications using low frequency alternating magnetic field

Iron oxide-based magnetic resonance imaging (MRI) contrast agents have negative contrast limitations in cancer diagnosis. Gadolinium (Gd)-based contrast agents show toxicity. To overcome these limitations, Gd-doped ferrite (Gd:Fe3O4 (GdIO) nanoparticles (NPs) were synthesized as T1-T2 dual-modal contrast agents for MRI-traced drug delivery. A theranostics GdIO encapsulated in a Generation 4.5 PAMAM dendrimer (G4.5-GdIO) was developed by alkaline coprecipitation. The drug-loading efficiency of the NPs was ∼24%. In the presence of a low-frequency alternating magnetic field (LFAMF), a maximum cumulative doxorubicin (DOX) release of ∼77.47% was achieved in a mildly acidic (pH = 5.0) simulated endosomal microenvironment. Relaxometric measurements indicated superior r1 (5.19 mM−1s−1) and r2 (26.13 mM−1s−1) for G4.5-GdIO relative to commercially available Gd-DTPA. Thus, G4.5-GdIO is promising as an alternative noninvasive MRI-traced cancer drug delivery system.

Magnetically targetable microcapsules display subtle changes in permeability and drug release in response to a biologically compatible low frequency alternating magnetic field

High frequency alternating magnetic fields (AMF) have been widely used as a non-invasive method to induce local hyperthermia for antitumor treatment and to efficiently trigger drug release from various carriers. However, few studies have exploited the potential of targeted drug delivery to healthy cells or tissue and the use of low frequency AMF (LF-AMF) for intracellular triggered release. To achieve this goal, doxycycline was delivered with the layer-by-layer (LbL) assembled magnetic microcapsules, and AMF with low frequency (50 Hz) was applied. The low frequency AMF had little effect on morphology of microcapsules, which upon exposure for 360 min caused no significant damage and had the advantage of minimizing heating effects. Nonetheless, microcapsule permeability increased as a function of exposure time when assessed using FITC-dextran (70 kDa) with the number of permeable microcapsules increased from 13.5% (20 min) to 52.8% (360 min). Increased permeability also enhanced in vitro doxycycline release in genetically engineered myoblast cells where EGFP expression is regulated by the tetracycline system, while targeted EGFP expression was observed by magnetically navigating the microcapsules to a site of interest. Upon LF-AMF exposure of 30 min, no cytotoxicity was observed, but intracellular doxycycline release was promoted and enhanced EGFP expression as demonstrated by EGFP fluorescence intensity measurement. This study reveals the possibility of targeted drug delivery and using LF-AMF as a non-cytotoxic intracellular trigger of drug release from microcapsules without alteration in cell viability.

Tough Magnetic Chitosan Hydrogel Nanocomposites for Remotely Stimulated Drug Release.

As one of important biomaterials for localized drug delivery system, chitosan hydrogel still suffer several challenges, including poor mechanical properties, passive drug release behavior and lack of remote stimuli response. To address these challenges, a facile in situ hybridization method was reported for fabricate tough magnetic chitosan hydrogel (MCH), which remotely switched drug release from passive release to pulsatile release under a low frequency alternating magnetic field (LAMF). The in situ hybridization method avoided the aggregation of magnetic nanoparticles (MNPs) in hydrogel, which simultaneously brings 416% and 265% increase in strength and elastic modulus, respectively. The mechanical property enhancement was contributed by the physical crosslinking of in situ synthesized MNPs. When a LAMF with 15 min ON-15 min OFF cycles was applied to MCH, the fraction release showed zigzag shape and pulsatile release behavior with quick response. The cumulative release and fraction release of drug from MCH were improved by 67.2% and 31.9%, respectively. MTT results and cell morphology indicated that the MCH have excellent biocompatibility and no acute adverse effect on MG-63 cells. The developed tough MCH system holds great potential for applications in smart drug release system with noninvasive characteristics and magnetic field stimulated drug release behavior.

The dynamics of magnetic nanoparticles exposed to non-heating alternating magnetic field in biochemical applications: theoretical study

In the past decade, magneto-nanomechanical approach to biochemical systems stimulation has been studied intensively. This method involves macromolecule structure local deformation via mechanical actuation of functionalized magnetic nanoparticles (f-MNPs) by non-heating low frequency (LF) alternating magnetic field (AMF). Specificity at cellular or molecular level and spatial locality in nanometer scale are its key advantages as compared to magnetic fluid hyperthermia. However, current experimental studies have weak theoretical basis. Several models of magneto-nanomechanical actuation of macromolecules and cells in non-heating uniform LF AMF are presented in the article. Single core-shell spherical, rod-like, and Janus MNPs, as well as dimers consisting of two f-MNPs with macromolecules immobilized on their surfaces are considered. AMF-induced rotational oscillations of MNPs can affect properties and functioning of macromolecules or cellular membranes attached to them via periodic deformations in nanometer scale. This could be widely used in therapy, in particular for targeted drug delivery, controlled drug release, and cancer cell killing. An aggregate composed of MNPs can affect associated macromolecules by force up to several hundreds of piconewton in the case of MNPs of tens of nanometers in diameter and LF AMF below 1 T. AMF parameters and MNP design requirements for effective in vitro and in vivo magneto-nanomechanical treatment are presented.

Tumor therapy by fast moving magnetic nanoparticle under low-frequency alternating magnetic field

Magnetic nanoparticle plays an important role in biomedical engineering, especially in tumor therapy. In this paper, a new technique has been developed by using the rapid moving magnetic nanoparticle under a low-frequency alternating magnetic field (LFAMF) to kill tumor cells. The LFAMF system which was used to drive magnetic nanoparticles (MNPs) was setup with the magnetic field frequency and power range at ∼ 10–100 Hz and ∼ 10–200 mT, respectively. During the experiment, the LFAMF was adjusted at different frequencies and power levels. The experimental results show that the liver tumor cells (HepG2) mixed with MNPs (10 μg/mL) became partial fragments when exposed in the LFAMF with different frequencies (∼ 10–100 Hz) and power (∼ 10–200 mT), and the higher the frequency or the power, the more the tumor cells were killed at the same magnetic nanoparticle concentration. Conclusion: Tumor cells were effectively damaged by MNPs under LFAMF, which suggests that they had great potential to be applied in tumor therapy.

Effect of Alternating Magnetic Field on the Microstructure and Solute Distribution of Cu&amp;ndash;14Fe Composites

The influence of a low frequency alternating magnetic field (LFAMF) during solidification was investigated for Cu-14Fe composites. The microstructure was investigated by optical microscope; the solute distribution in different phases was analyzed by scanning electron microscopy and energy-dispersive X-ray spectroscopy; the oxygen content was tested by oxygen & nitrogen analyzer; the conductivity was measured by eddy current conductivity meter; and the micro-hardness was measured by Vickers hardness tester. AMF treatment reduced rod shape and large size Fe dendrites, changed some Fe dendrites into club shape and equiaxed grains, and promoted the homogenization of Fe phase distribution. In addition, AMF treatment increased the Cu content in Fe phase and decreased the Fe content in Cu matrix. The effect of AMF during solidification was discussed from the view of thermodynamics and kinetics. This was attributed to the refinement of primary Fe dendrites and the precipitation of Fe atoms from Cu matrix.

Magnetocubosomes for the delivery and controlled release of therapeutics

The design of nanostructured drug delivery systems (DDS) that improve the efficacy of therapeutic principles by enhancing their biocompatibility, bioavailability and targeting, has been the focus of extensive research over the past years. Of particular relevance in this field is the development of multifunctional architectures that can deliver different therapeutics or diagnostic agents and release them in a controlled way. In this study we report on the design, preparation and characterization of a DDS where hydrophobic Fe3O4 magnetic nanoparticles (NPs) are included in the bilayer of bicontinuous cubic lipid nanoparticles of Glyceryl Monooleate (GMO). The “magnetocubosomes” are characterized and investigated in terms of their ability to encapsulate and release both hydrophilic and hydrophobic model drugs. For the first time Fluorescence Correlation Spectroscopy (FCS) is used to study the diffusion of encapsulated molecules inside the bicontinuous cubic phase and to monitor their release from the matrix towards the aqueous phase. In addition, we show with the same technique that magnetocubosomes are responsive to a low frequency alternating magnetic field (LF-AMF), which acts as an external trigger to boost the release of model drugs confined in the cubic phase. Magnetocubosomes, reported for the first time in this paper, represent a novel biocompatible, multifunctional and responsive DDS.

Theranostic magnetoliposomes coated by carboxymethyl dextran with controlled release by low-frequency alternating magnetic field.

The aim of this work was to construct carboxymethyl dextran (CMD)-coated magnetoliposomes (MLs), another stealth MLs alternative to PEGylated MLs, for theranostic application. Particularly, the on-demand release of CMD-MLs under low-frequency alternating magnetic field (LF-AMF) was studied. We found that as-prepared MLs exhibited good stability and high drug loading ability for doxorubicin (DOX). Cytotoxicity assay against human neuroblastoma SH-SY5Y cells showed that the DOX-loaded CMD-MLs were less toxic than free DOX due to the sustained release of DOX. However, the release of DOX-loaded CMD-MLs was enhanced by low-frequency alternating magnetic field without hyperthermia generation. The MLs also acted as an efficient T2-weighted contrast agent during in vitro MRI measurements. The above results provide useful information on in vivo diagnostic/therapeutic efficacy of DOX-loaded CMD-MLs for some cancers, such as brain cancers.

The effect of solution heat treatments on the microstructure and hardness of ZK60 magnesium alloys prepared under low-frequency alternating magnetic fields

The solidified structure of ZK60 magnesium alloys in the presence and absence of electromagnetic stirring during the solidification process was compared, and the precipitates of ZK60 magnesium alloys were analyzed after a solution heat treatment using optical microscopy, micro-hardness analysis, X-ray diffraction and scanning electron microscopy. The results showed that the microstructure of cast alloys under a low-frequency alternating magnetic field (LFAMF) was mainly composed of a primary crystalline Mg matrix and a non-equilibrium eutectic structure (Mg+MgZn+MgZn2). In comparison with the microstructure observed in the absence of the electromagnetic field, the eutectic network structure on the grain boundary under low-frequency alternating magnetic field was finer and exhibited a more uniform grain distribution. The grains under the LFAMF were refined in comparison with those under no electromagnetic field before the solution heat treatment, and the former grain distribution was more uniform than the latter after the solution heat treatment. The more uniform grain distribution is because the solution heat treatment is conducive to the dissolution of the second phase particles. The hardness exhibited a downward trend with increasing solution heat treatment time. Under the same solution heat treatment, the hardness value of the samples prepared under the LFAMF was lower than those prepared in the absence of the electromagnetic field. In contrast, the mechanical properties of alloys prepared under the LFAMF were better than those prepared in the absence of the electromagnetic field.

Controlled drug release under a low frequency magnetic field: effect of the citrate coating on magnetoliposomes stability

The paper describes the effect of a low-frequency alternating magnetic field (LF-AMF) on the permeability and release properties of large (LUVs) and giant (GUVs) unilamellar vesicles loaded with citrate coated cobalt ferrite nanoparticles (NPs). The citrate shell allows a high loading of NPs in lipid vesicles without modifying their magnetic properties. The increase of magnetic LUVs permeability upon exposure to LF-AMF has been evaluated as the fluorescence self-quenching of carboxyfluorescein (CF) entrapped inside the liposome aqueous pool. Liposome leakage has been monitored as a function of field frequency, time exposure and concentration of the citrate coated NPs. Confocal Laser Scanning Microscopy (CLSM) experiments performed on magnetic GUVs labeled with the fluorescent probe DiIC18 and loaded with Alexa 488-C5-maleimide fluorescent dye provided insights on the release mechanism induced by LF-AMF. The results show that LF-AMF strongly affects vesicles permeability, suggesting the formation of pores in the lipid bilayer due to both hyperthermic effects and nanoparticle oscillations in the vesicles pool at the applied frequency. The behaviour of these magnetic vesicles in the presence of LF-AMF makes this system a good candidate for controlled drug delivery.

Structure and permeability of magnetoliposomes loaded with hydrophobic magnetic nanoparticles in the presence of a low frequency magnetic field

In this paper we describe the effect of a low frequency alternating magnetic field (LF-AMF) on the structure and permeability of magnetoliposomes, i.e. liposomes formulated in the presence of magnetic nanoparticles. Hydrophobic cobalt ferrite nanoparticles (CoFe2O4) coated with a shell of oleic acid were prepared, characterized and employed in the preparation of magnetoliposomes. The stability of the lipid bilayer after the application of an oscillating magnetic field was studied by means of Dynamic Light Scattering (DLS), Small Angle Scattering of X-rays (SAXS) and Differential Scanning Calorimetry (DSC). The enhancement of liposome permeability upon LF-AMF exposure was measured as the self-quenching decrease of the fluorescent molecule carboxyfluorescein (CF) entrapped in the liposome pool. Carboxyfluorescein leakage from magnetoliposomes was investigated as a function of field frequency, time of exposure to the magnetic field, and cobalt ferrite nanoparticles concentration. Kinetics of CF release from LF-AMF treated magnetoliposomes, monitored through the fluorescence intensity increase during time, highlights a slow release of CF during the first hours, followed by a faster release a few hours after the field treatment which leads to a complete leakage of CF. DSC provides insights about the effect of the LF-AMF treatment, showing that the first few hours correspond to a complete loss of the transition peak from the lamellar gel (Lβ) phase to the liquid crystalline (Lα) phase of the PC bilayers. These results suggest that the slow release takes place through the formation of local pores or defects at the membrane level, while the fast release corresponds to an increased permeability of the membrane that can be related to a structural change of the bilayer.

Magnetoliposomes for controlled drug release in the presence of low-frequency magnetic field

In this work we have studied the effect of a low-frequency alternating magnetic field (LF-AMF) on the permeability of magnetoliposomes, i.e. liposomes including magnetic nanoparticles within their water pool. Large unilamellar liposomes loaded with magnetic cobalt ferrite nanoparticles (CoFe2O4) have been prepared and characterized. Structural characterization of the liposomal dispersion has been performed by dynamic light scattering (DLS). The enhancement of liposome permeability upon exposure to LF-AMF has been measured as the self-quenching decrease of a fluorescent hydrophilic molecule (carboxyfluorescein, CF) entrapped in the liposome pool. Liposome leakage has been monitored as a function of field frequency, time of exposure and concentration, charge and size of the embedded nanoparticles. The results show that CF release from magnetoliposomes is strongly promoted by LF-AMF, reasonably as a consequence of nanoparticle motions in the liposome pool at the applied frequency. CF release as a function of time in magnetoliposomes unexposed to magnetic field follows Fickian diffusion, while samples exposed to LF-AMF show zero-order kinetics, consistently with an anomalous transport, due to an alteration of the bilayer permeability. These preliminary results open up new perspectives in the use of these systems as carriers in targeted and controlled release of drugs.