In vitro study of magnetic particle seeding for implant assisted-magnetic drug targeting

The concept of using magnetic particles (seeds) as the implant for implant assisted-magnetic drug targeting (IA-MDT) was analyzed in vitro. Since this MDT system is being explored for use in capillaries, a highly porous (ε∼70%), highly tortuous, cylindrical, polyethylene polymer was prepared to mimic capillary tissue, and the seeds (magnetite nanoparticles) were already fixed within. The well-dispersed seeds were used to enhance the capture of 0.87 μm diameter magnetic drug carrier particles (MDCPs) (polydivinylbenzene embedded with 24.8 wt% magnetite) under flow conditions typically found in capillary networks. The effects of the fluid velocity (0.015–0.15 cm/s), magnetic field strength (0.0–250 mT), porous polymer magnetite content (0–7 wt%) and MDCP concentration (C=5 and 50 mg/L) on the capture efficiency (CE) of the MDCPs were studied. In all cases, when the magnetic field was applied, compared to when it was not, large increases in CE resulted; the CE increased even further when the magnetite seeds were present. The CE increased with increases in the magnetic field strength, porous polymer magnetite content and MDCP concentration. It decreased only with increases in the fluid velocity. Large magnetic field strengths were not necessary to induce MDCP capture by the seeds. A few hundred mT was sufficient. Overall, this first in vitro study of the magnetic seeding concept for IA-MDT was very encouraging, because it proved that magnetic particle seeds could serve as an effective implant for MDT systems, especially under conditions found in capillaries.     

Theoretical analysis of a transdermal ferromagnetic implant for retention of magnetic drug carrier particles

The use of a ferromagnetic wire implant placed near an artery to assist the collection of magnetic drug carrier particles (MDCPs) using an external magnet is theoretically studied. Three magnetic drug targeting (MDT) systems are evaluated in terms of their MDCP collection efficiency (CE): a permanent magnet and wire is better than a permanent magnet alone, which is better than a homogeneous magnetic field and wire.     

Quantification of drug-loaded magnetic nanoparticles in rabbit liver and tumor after in vivo administration

Magnetic nanoparticles have been investigated for biomedical applications for more than 30 years. The development of biocompatible nanosized drug delivery systems for specific targeting of therapeutics is imminent in medical research, especially for treating cancer and vascular diseases. We used drug-labeled magnetic iron oxide nanoparticles, which were attracted to an experimental tumor in rabbits with an external magnetic field (magnetic drug targeting, MDT). Aim of this study was to detect and quantify the biodistribution of the magnetic nanoparticles by magnetorelaxometry. The study shows higher amount of nanoparticles in the tumor after intraarterial application and MDT compared to intravenous administration.     

Detection of magnetic nanoparticles with magnetoencephalography

Superconducting quantum interference devices (SQUIDs) have been widely utilized in biomedical applications due to their extremely high sensitivity to magnetic signals. The present study explores the feasibility of a new type of nanotechnology-based imaging method using standard clinical magnetoencephalographic (MEG) systems equipped with SQUID sensors. Previous studies have shown that biological targets labeled with non-toxic, magnetized nanoparticles can be imaged by measuring the magnetic field generated by these particles. In this work, we demonstrate that (1) the magnetic signals from certain nanoparticles can be detected without magnetization using standard clinical MEG, (2) for some types of nanoparticles, only bound particles produce detectable signals, and (3) the magnetic field of particles several hours after magnetization is significantly stronger than that of un-magnetized particles. These findings hold promise in facilitating the potential application of magnetic nanoparticles to in vivo tumor imaging. The minimum amount of nanoparticles that produce detectable signals is predicted by theoretical modeling and computer simulation.     

Bioavailability of magnetic nanoparticles to the brain

This study investigates the bioavailability of carboxymethyl dextran-coated magnetic nanoparticles (CMD-MNP) to the brain. The cytotoxicity of CMD-MNP was assessed by co-culture with C6, a rat glioma cell line. To investigate the effects of an external magnetic field on the biodistribution of nanoparticles in a rat model, a magnet of 0.3 Tesla was applied externally over the cranium and the particles injected via the external jugular vein. Nanoparticles were also injected into rats implanted with C6 tumor cells. Staining of histological samples with Prussian blue to detect iron particles revealed that the external magnetic field enhanced the aggregation of nanoparticles in the rat brain; this enhancement was even more pronounced in the tumor region.     

Quantitative targeting maps based on experimental investigations for a branched tube model in magnetic drug targeting

Magnetic drug targeting (MDT), because of its high targeting efficiency, is a promising approach for tumour treatment. Unwanted side effects are considerably reduced, since the nanoparticles are concentrated within the target region due to the influence of a magnetic field. Nevertheless, understanding the transport phenomena of nanoparticles in an artery system is still challenging. This work presents experimental results for a branched tube model. Quantitative results describe, for example, the net amount of nanoparticles that are targeted towards the chosen region due to the influence of a magnetic field. As a result of measurements, novel drug targeting maps, combining, e.g. the magnetic volume force, the position of the magnet and the net amount of targeted nanoparticles, are presented. The targeting maps are valuable for evaluation and comparison of setups and are also helpful for the design and the optimisation of a magnet system with an appropriate strength and distribution of the field gradient. The maps indicate the danger of accretion within the tube and also show the promising result of magnetic drug targeting that up to 97% of the nanoparticles were successfully targeted.     

Site-directed research of magnetic nanoparticles in magnetic drug targeting

The targeting of ferrofluids composed of 20 nm magnetic particles was studied through simulation and animal experiment. The results showed that some magnetic particles were concentrated in the target area depending on the applied magnetic field. Through theoretical analysis, the retention of the magnetic nanoparticles in a target area is due to large magnetic liquid beads formed by the magnetic field.     

Thermosensitive magnetic polymer particles as contactless controllable drug carriers

Spherically shaped thermosensitive micro and nanoparticles based on N-isopropylacrylamide were synthesized using a novel inverse suspension polymerization technique which enables a bead formation within minutes. In addition to the rapidity, the suspension procedure provides an effective platform for the encapsulation of magnetic colloids and simultaneous drug analogous substances. The presence of the magnetic colloids allows an inductive heating of the particles using an alternating magnetic field above the polymer transition temperature (>35 °C). This results in a pronounced de-swelling accompanied by a release of the encapsulated substances. The potential of this technology for a new contactless controllable drug releasing approach is exemplarily demonstrated using rhodamine B and methylene blue as drug analogous substances.     

Experimental investigations on a branched tube model in magnetic drug targeting

Magnetic drug targeting (MDT) has been established as a promising technique for tumour treatment. Due to its high targeting efficiency unwanted side effects are considerably reduced, since drug-loaded nanoparticles are concentrated within a target region due to the influence of a magnetic field. This work presents experimental results that are based on systematic quantitative measurements on a branched tube model as a model system for a blood vessel supplying a tumour. The systematic measurements are summarized in novel drug targeting maps, combining e.g. the net amount of targeted nanoparticles, the magnetic volume force and also the position of the magnet. The model, the injection procedure and the ferrofluid are chosen close to the parameters of a medical application. This will allow transfer of the results to future medical investigations. This work will present a targeting map, where the concentration of the injected ferrofluid is in the range of experiments with an ex vivo bovine artery model.     

Magnetic nanoparticles for local drug delivery using magnetic implants

Magnetic nanoparticles are good candidates used for the targeted delivery of anti-tumor agents. They can be concentrated on a desired region, reducing collateral effects and improving the efficiency of the chemotherapy. We propose a method in which permanent magnets are implanted by laparoscopic technique directly in the affected organ. This method proposes the use of Fe@C nanoparticles, which are loaded with doxorubicin and injected intravenously. The particles, once attracted to the magnet, release the drug at the tumor region. This method seems to be more promising and effective than that based on the application of external magnetic fields.     

Monte Carlo study of small magnetic particles

In earlier computer simulation small magnetic particles with nearest neighbor Heisenberg interactions in zero magnetic field have been studied. We now continue these investigations including next nearest neighbor exchange and non zero magnetic fieldsH. The particles treated have spherical shape with a number of spinsN in the range from 33 to 3071. It is shown that the spontaneous magnetization of the particles is rather different from the bulk magnetization. The magnetization process can be accounted for by the Néel theory, if the correct spontaneous magnetization of the particle is used. The distribution of local magnetizations (the magnetic “profile”) was also obtained in various cases. It is shown that the magnetization of very small particles is much more depressed than predicted by the mean field approximation. We introduce an “effective magnetic radius” \(\hat R\) accounting for the reduction of the local magnetization. This magnetic radius is important for the interpretation of experimental results. A distinct dependence of \(\hat R\) on the magnetic field, temperature and the fraction of next nearest neighbor exchange is found. Finally a brief comparison is made with the recent study of magnetic surface properties by Binder and Hohenberg.     

Biodegradable nanocomposite magnetite stent for implant-assisted magnetic drug targeting

This study shows, for the first time, the fabrication of a biodegradable polymer nanocomposite magnetic stent and the feasibility of its use in implant-assisted-magnetic drug targeting (IA-MDT). The nanocomposite magnetic stent was made from PLGA, a biodegradable copolymer, and iron oxide nanopowder via melt mixing and extrusion into fibers. Degradation and dynamic mechanical thermal analyses showed that the addition of the iron oxide nanopowder increased the polymer’s glass transition temperature (T_g) and its modulus but had no notable effect on its degradation rate in PBS buffer solution. IA-MDT in vitro experiments were carried out with the nanocomposite magnetic fiber molded into a stent coil. These stent prototypes were used in the presence of a homogeneous magnetic field of 0.3 T to capture 100 nm magnetic drug carrier particles (MDCPs) from an aqueous solution. Increasing the amount of magnetite in the stent nanocomposite (0, 10 and 40 w/w%) resulted in an increase in the MDCP capture efficiency (CE). Reducing the MDCP concentrations (0.75 and 1.5 mg/mL) in the flowing fluid and increasing the fluid velocities (20 and 40 mL/min) both resulted in decrease in the MDCP CE. These results show that the particle capture performance of PLGA-based, magnetic nanocomposite stents are similar to those exhibited by a variety of different non-polymeric magnetic stent materials studied previously.     

Spatial variation of superconducting properties of Gd123 Bulk superconductors with magnetic particles addition

Magnetic flux trapping and the homogeneity of the flux pinning are essential problems in the practical application of high-temperature superconductors. We have conducted study on the role of addition of soft magnetic Fe-B alloy particles contribute to the enhancement of the critical current density (J_c) under wide-range of magnetic field. Magnetic flux trapping was enhanced in Gd123 bulk superconductor with suitable amount of magnetic particles addition. In addition, it can be effective as pinning center enhance the J_c of the bulk in both the a–b growth sector and the c-growth sector under magnetic field. However, the T_c of the Gd123 bulk was decreased obviously by addition of magnetic particles. The study on the spatial variation of superconducting properties indicates that the performance of the upper part of the bulk is better than the bottom. By comparing the superconducting properties of the Gd123 bulk with magnetic particles addition and without magnetic particles addition, we concluded that there is a trace of the formation of homogeneous pinning properties in the magnetic particles addition Gd123 bulk.     

Manipulation of magnetic carriers for drug delivery using pulsed-current high Tc superconductors

An innovative method of manipulating magnetic carriers is proposed, and its feasibility for drug delivery and therapy is demonstrated experimentally. The proposed method employs pulsed-field solenoid coils with high-critical- temperature (T_c) superconductor inserts. Pulsed current is used to magnetize and de-magnetize the superconductor insert. The proposed method was demonstrated to be able to (1) move magnetic particles, ranging in size from a few millimeters to 10 μm, with strong enough forces over a substantial distance, (2) hold the particles at a designated position as long as needed, and (3) reverse the processes and retrieve the particles. We further demonstrated that magnetic particles can be manipulated in a stationary environment, in water flow, and in simulated blood (water/glycerol mixture) flow.     

Multiparametric magnetic immunoassays utilizing non-linear signatures of magnetic labels

A powerful route to utilizing magnetic nanoparticles as labels in magnetic immunoassays is to exploit their non-linear response when they are exposed to a multi-frequency alternating magnetic field. We have upgraded this non-linear method allowing for the detection, discrimination and quantification of particles of two kinds when mixed together, with no need for spatial resolution. Each kind of particle is characterized by a specific magnetic signature based on d²B(H)/dH². Appropriate data processing of the signature measured on a mixture of both particles allows for obtaining the amount of each particle. This will enable utilizing magnetic labels for multiparametric magnetic immunoassays.     

In vitro study of magnetic particle seeding for implant-assisted-magnetic drug targeting: Seed and magnetic drug carrier particle capture

An implant-assisted-magnetic drug targeting system using seed particles as the implant to increase the capture of magnetic drug carrier particles (MDCPs) in capillary tissue was studied in vitro. Dextran-coated magnetite particles were used as seeds, polydivinylbenzene magnetite particles were used as MDCPs, and a polyethylene porous cylinder was used as surrogate capillary tissue. The results showed that seeds could be magnetically captured first and then used to magnetically capture the MDCPs, causing a significant increase in their collection compared to when the seeds were absent.     

In vitro study of magnetic nanoparticles as the implant for implant assisted magnetic drug targeting

Magnetic nanoparticle (MNP) seeds were studied in vitro for use as an implant in implant assisted-magnetic drug targeting (IA-MDT). The magnetite seeds were captured in a porous polymer, mimicking capillary tissue, with an external magnetic field (70 mT) and then used subsequently to capture magnetic drug carrier particles (MDCPs) (0.87 μm diameter) with the same magnetic field. The effects of the MNP seed diameter (10, 50 and 100 nm), MNP seed concentration (0.25-2.0 mg/mL), and fluid velocity (0.03-0.15 cm/s) on the capture efficiency (CE) of both the MNP seeds and the MDCPs were studied. The CE of the 10 nm MNP seeds was never more than 30%, while those of the 50 and 100 nm MNP seeds was always greater than 80% and in many cases exceeded 90%. Only the MNP seed concentration affected its CE. The 10 nm MNP seeds did not increase the MDCP CE over that obtained in the absence of the MNP seeds, while the 50 and 100 nm MNP seeds increased significantly, typically by more than a factor of two. The 50 and 100 nm MNP seeds also exhibited similar abilities to capture the MDCPs, with the MDCP CE always increasing with decreasing fluid velocity and generally increasing with increasing MNP seed concentration. The MNP seed size, magnetic properties, and capacity to self-agglomerate and form clusters were key properties that make them a viable implant in IA-MDT.     

On the theory of rheological properties of magnetic suspensions

The paper deals with a theoretical study of influence of magnetic field on effective viscosity of suspension of non-Brownian magnetizable particles. It is supposed that experimentally observed magnetorheological effects are provided by chain-like aggregates, consisting of the particles. Unlike previous works on this subject, we take into account that the chains cannot be identical and estimate their size distribution. The following power law (η-η₀)/η₀∼Mn^-Δ, detected in many experiments, is obtained theoretically (η and η₀ are the suspension effective viscosity and the carrier liquid viscosity, respectively, Mn is the so-called Mason number, proportional to the shear rate and inversely proportional to the square of magnetic field). The calculated magnitude of the exponent Δ increases with the applied magnetic field from approximately 0.66 to 0.8-0.9 and slowly increases with the volume concentration ? of the particles. These results are in agreement with known experiments.     

Particle size effect on phase and magnetic properties of polymer-coated magnetic nanoparticles

Polymer-coated magnetic nanoparticles are hi-tech materials with ample applications in the field of biomedicine for the treatment of cancer and targeted drug delivery. In this study, magnetic nanoparticles were synthesized by chemical reduction of FeCl₂ solution with sodium borohydride and coated with amine-terminated polyethylene glycol (aPEG). By varying the concentration of the reactants, the particle size and the crystallinity of the particles were varied. The particle size was found to increase from 6 to 20 nm and the structure becomes amorphous-like with increase in the molar concentration of the reactant. The magnetization at 1 T field (M_1T) for all samples is > 45 emu/g while the coercivity is in the range of 100-350 Oe. When the ethanol-suspended particles are subjected to an alternating magnetic field of 4 Oe at 500 kHz, the temperature is increased to a maximum normalized temperature (3.8 °C/mg) with decreasing particle size.     

A model for predicting magnetic targeting of multifunctional particles in the microvasculature

A mathematical model is presented for predicting magnetic targeting of multifunctional carrier particles that are designed to deliver therapeutic agents to malignant tissue in vivo. These particles consist of a nonmagnetic core material that contains embedded magnetic nanoparticles and therapeutic agents such as photodynamic sensitizers. For in vivo therapy, the particles are injected into the vascular system upstream from malignant tissue, and captured at the tumor using an applied magnetic field. The applied field couples to the magnetic nanoparticles inside the carrier particle and produces a force that attracts the particle to the tumor. In noninvasive therapy, the applied field is produced by a permanent magnet positioned outside the body. In this paper, a mathematical model is developed for predicting noninvasive magnetic targeting of therapeutic carrier particles in the microvasculature. The model takes into account the dominant magnetic and fluidic forces on the particles and leads to an analytical expression for predicting their trajectory. An analytical expression is also derived for predicting the volume fraction of embedded magnetic nanoparticles required to ensure capture of the carrier particle at the tumor. The model enables rapid parametric analysis of magnetic targeting as a function of key variables including the size of the carrier particle, the properties and volume fraction of the embedded magnetic nanoparticles, the properties of the magnet, the microvessel, the hematocrit of the blood and its flow rate.