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.     

Preparation of a biocompatible magnetic film from an aqueous ferrofluid

Very promising nanoparticles for biomedical applications or in medical drug targeting are superparamagnetic nanoparticles based on a core consisting of iron oxides (SPION) that can be targeted through external magnets. Polyvinyl alcohol (PVA) is a unique synthetic biocompatible polymer that can be chemically cross-linked to form a gel. Biotechnology applications of magnetic gels include biosensors, targeted drug delivery, artificial muscles and magnetic buckles. These gels are produced by incorporating magnetic materials in the polymer composites. In this paper we report the synthesis of an aqueous ferrofluid and the preparation of a biocompatible magnetic gel with polyvinyl alcohol and glutharaldehyde (GTA). HClO₄ was used to induce the peptization since this kind of ferrofluid does not have surfactant. The magnetic gel was dried to generate a biocompatible film.     

In vitro investigation of the behaviour of magnetic particles by a circulating artery model

Magnetic drug targeting is the use of coated magnetic nanoparticles as carriers for cytostatic drugs. After intraarterial application of these carriers, they are attracted with an external magnetic field to, for example, an experimental VX2 tumour. The biological compatibility of this system depends on several physiological and physical parameters. We established an in vitro model to simulate in vivo conditions in a circulating system consisting of a circuit with an intact bovine femoral artery close to an external magnetic field. Nanoparticle suspensions were applied by a side inlet. After the magnetisation procedure particle size, concentration and distribution was examined.     

In vitro and in vivo investigations of targeted chemotherapy with magnetic nanoparticles

Magnetic drug targeting is a local drug delivery system. Electromicroscopic pictures document the ferrofluid enrichment in the intracellular space in vitro. In vivo experiments were performed in VX2 tumor-bearing rabbits using magnetic nanoparticles bound to mitoxantrone. High-pressure liquid chromatography (HPLC) analyses after magnetic drug targeting showed an increasing concentration of the chemotherapeutic agent in the tumor region compared to regular systemic chemotherapy.     

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.     

Experimental investigation for enhanced ferrofluid heat transfer under magnetic field effect

This paper reports an experimental work on the convective heat transfer of ferrofluid flowing through a heated copper tube in the laminar regime in the presence of magnetic field. Significant enhancement on the heat transfer of ferrofluid by applying various orders of magnetic field is observed in this experiment. Also in this experiment, the effect of magnetic nanoparticles concentrations and magnet position have been investigated. The main reason for the enhancement of heat transfer coefficient could be caused due to remarkable changes in thermophysical properties of ferrofluid under the influence of applied magnetic field.     

Reciprocity of Faraday effect in ferrofluid: Comparison with magneto-optical glass

The transmission light intensity method is carried out on a classical platform to study the reciprocity of Faraday effect in water-based Fe₃O₄ ferrofluid and its diluents. Setting the polarization direction of the analyzer at an angle of 45° to that of the polarizer, the switchable DC magnetic field and the alternating magnetic field are imposed to ferrofluid. The ferrofluid film is replaced by magneto-optical glass for contrastive experiments. The results indicate that ferrofluid is different with magneto-optical glass. Even though the direction of magnetic field is reversed, the rotation direction of the polarized light does not change for ferrofluid. The theoretical model of magneto-optical rotation was used to describe the origin of the reciprocity of Faraday effect in ferrofluid and the non-reciprocity in magneto-optical glass. These findings suggest that the magnetic moments of nanoparticles in ferrofluid tend to the same orientation with the magnetic field because of the rotation of particles.     

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.     

梯度磁场作用下光纤中磁流体光透射特性研究的建模与分析

对光纤中磁流体在梯度磁场作用下的光透射特性进行了研究,提出光纤中磁流体的光透射率变化主要来源于梯度磁场引起的磁流体密度分布变化。根据郎之万函数和流体理论,推导了光纤中磁流体在梯度磁场作用下的密度分布,并根据Beer-Lambert定律,得到磁流体光功率透射衰减和纳米粒子局部密度的关系,从而建立光纤中磁流体在梯度磁场作用下光透射特性的理论模型。进而对光纤中磁流体在不同梯度磁场作用下的光透射功率进行数值分析,得到不同磁场强度和磁场梯度下光纤中磁流体透射功率的变化规律。最后将数值分析的结果和实验数据进行对比,验证了模型的合理性, 同时也验证了梯度磁场作用下磁流体光透射功率的变化主要来源于磁流体密度分布变化的推论。     

磁流体流动与传热的格子Boltzmann模拟

考虑外加磁场下磁流体中纳米磁性粒子所受的各种作用力,建立了用于模拟磁流体流动与传热特性的两相格子Boltzmann模型,模拟了外加不同方向梯度磁场下平板间磁流体的流动与传热过程,计算了磁流体与平板间对流换热的Nusselt数,分析了磁场梯度方向、大小对Nusselt数的影响．     

Microstructure of bidisperse ferrofluids in a thin layer

In this work we present a characterization of the bidisperse ferrofluid microstructures that appear in thin layers of ferrofluid. These layers have been studied by a combination of Langevin dynamics simulations and density functional theory. Our results allow us to compare the microstructures that exist in quasi-two-dimensional ferrofluid nanolayers with the microstructures found in three-dimensional bidisperse ferrofluids. Furthermore, our results allow us to explain the influence of the geometry of the sample on the topology and size-distribution of the observed aggregates of magnetic nanoparticles.     

CFD study on the magnetic fluid delivering in the vessel in high-gradient magnetic field

This paper simulated the advection and diffusion behaviors of the moving magnetic fluid in the vessel in the high-gradient magnetic field using Navier–Stokes equations. The particles accumulation behavior and the streamlines and the contour of concentration are all affected by the susceptibility, intensity of magnetic field and its gradient, and the flow velocity and also by the difference in size of vessels. The typical accumulation behaves as a solid obstacle in the flow as result of the competing between magnetic and fluid drag forces, and gives rise to a rigidly bound core region followed by a wash away region near the vessel boundary under the condition of 10 mm vessel in width. While the vessel is near 1 mm in width, the magnetic force is exerted almost on the whole vessel area, the vortex is not seen, the wash away area disappears and the concentration changes in the whole vessel. The results of the analysis provide meaningful information on ferrofluid transport and stabilization for various magnetic drug targeting and the magnetic fluid sealing, and other use in industrial and medical fields.     

Frequency-domain birefringence measurement of biological binding to magnetic nanoparticles

Optical detection of the frequency-dependent magnetic relaxation signal is used to monitor the binding of biological molecules to magnetic nanoparticles in a ferrofluid. Biological binding reactions cause changes in the magnetic relaxation signal due to an increase in the average hydrodynamic diameter of the nanoparticles. To allow the relaxation signal to be detected in dilute ferrofluids, measurements are made using a balanced photodetector, resulting in a 25 μV/√Hz noise floor, within 50% of the theoretical limit imposed by photon shot noise. Measurements of a ferrofluid composed of magnetite nanoparticles coated with anti-IgG antibodies show that the average hydrodynamic diameter increases from 115.2 to 125.4 nm after reaction with IgG.     

Preparation of composite with silica-coated nanoparticles of iron oxide spinels for applications based on magnetically induced hyperthermia

It is reported a novel method to prepare magnetic core (iron oxide spinels)–shell (silica) composites containing well-dispersed magnetic nanoparticles in aqueous solution. The synthetic process consists of two steps. In a first step, iron oxide nanoparticles obtained through co-precipitation are dispersed in an aqueous solution containing tetramethylammonium hydroxide; in a second step, particles of this sample are coated with silica, through hydrolyzation of tetraethyl orthosilicate. The intrinsic atomic structure and essential properties of the core–shell system were assessed with powder X-ray diffraction, Fourier transform infrared spectrometry, Mössbauer spectroscopy and transmission electron microscopy. The heat released by this ferrofluid under an AC-generated magnetic field was evaluated by following the temperature evolution under increasing magnetic field strengths. Results strongly indicate that this ferrofluid based on silica-coated iron oxide spinels is technologically a very promising material to be used in medical practices, in oncology.     

Magnetic lipid nanoparticles loading doxorubicin for intracellular delivery: Preparation and characteristics

Tumor intracellular delivery is an effective route for targeting chemotherapy to enhance the curative effect and minimize the side effect of a drug. In this study, the magnetic lipid nanoparticles with an uptake ability by tumor cells were prepared dispersing ferroso-ferric oxide nanoparticles in aqueous phase using oleic acid (OA) as a dispersant, and following the solvent dispersion of lipid organic solution. The obtained nanoparticles with 200 nm volume average diameter and −30 mV surface zeta potential could be completely removed by external magnetic field from aqueous solution. Using doxorubicin (DOX) as a model drug, the drug-loaded magnetic lipid nanoparticles were investigated in detail, such as the effects of OA, drug and lipid content on volume average diameter, zeta potential, drug encapsulation efficiency, drug loading, and in vitro drug release. The drug loading capacity and encapsulation efficiency were enhanced with increasing drug or lipid content, reduced with increasing OA content. The in vitro drug release could be controlled by changing drug or lipid content. Cellular uptake by MCF-7 cells experiment presented the excellent internalization ability of the prepared magnetic lipid nanoparticles. These results evidenced that the present magnetic lipid nanoparticles have potential for targeting therapy of antitumor drugs.     

Tomographic examination of magnetic nanoparticles used as drug carriers

Tumors grown on animals and treated with magnetic drug targeting and magnetic hyperthermia have been analyzed by microcomputed X-ray tomography to study the three-dimensional nanoparticle distribution. The measurements have been performed in two laboratories, with a polychromatic X-ray cone beam as well as with monochromatic parallel beam. Due to the poor resolution in the first case, the distribution of the magnetic nanoparticles can be studied only qualitatively. With the polychromatic beam semi-quantitative results can be achieved. In this paper, the results from both methods are presented and compared.     

Synthesis and characterization of tat-mediated O-CMC magnetic nanoparticles having anticancer function

This paper describes a new formulation of magnetic nanoparticles coated by a novel polymer matrix—O-carboxylmethylated chitosan (O-CMC) as drug/gene carrier. The O-CMC magnetic nanoparticles were derivatized with a peptide sequence from the HIV-tat protein to improve the translocational property and cellar uptake of the nanoparticles. To evaluate the O-MNPs-tat as drug carriers, MTX was incorporated as a model drug and MTX-loaded O-MNPs-tat with an average diameter of 45–60 nm were prepared and characterized by TEM, AFM and VSM. The cytotoxicity of MTX-loaded O-MNPs-tat was investigated with U-937 tumor cells. The results showed that the MTX-loaded O-MNPs-tat retained significant antitumor toxicity; additionally, sustained release of MTX from O-CMC nanoparticles was observed in vitro, suggesting that the tat-O-MNPs could be a novel magnetic targeting carrier.     

引导磁场下磁性药物靶向治疗的理论分析

应用电磁场理论，对引导磁场下铁磁性“药物”颗粒在靶向治疗中的受力和运动轨迹进行了分析和研究.得到了磁场、血流和血管壁对铁磁性“药物”颗粒的作用及运动规律.给出了铁磁性“药物”在靶向治疗中可采用的一种新方法——利用体外磁激励装置产生的变化磁场来实现铁磁性“药物”靶向治疗，还给出了采用这种方法实现靶向治疗的条件. 关键词： 磁性药物 靶向治疗 血流动力学 引导磁场     

Optimal Halbach permanent magnet designs for maximally pulling and pushing nanoparticles

Optimization methods are presented to design Halbach arrays to maximize the forces applied on magnetic nanoparticles at deep tissue locations. In magnetic drug targeting, where magnets are used to focus therapeutic nanoparticles to disease locations, the sharp fall off of magnetic fields and forces with distances from magnets has limited the depth of targeting. Creating stronger forces at a depth by optimally designed Halbach arrays would allow treatment of a wider class of patients, e.g. patients with deeper tumors. The presented optimization methods are based on semi-definite quadratic programming, yield provably globally optimal Halbach designs in 2 and 3-dimensions, for maximal pull or push magnetic forces (stronger pull forces can collect nanoparticles against blood forces in deeper vessels; push forces can be used to inject particles into precise locations, e.g. into the inner ear). These Halbach designs, here tested in simulations of Maxwell's equations, significantly outperform benchmark magnets of the same size and strength. For example, a 3-dimensional 36 element 2000 cm³ volume optimal Halbach design yields a 5× greater force at a 10 cm depth compared to a uniformly magnetized magnet of the same size and strength. The designed arrays should be feasible to construct, as they have a similar strength (≤1 T), size (≤2000 cm³), and number of elements (≤36) as previously demonstrated arrays, and retain good performance for reasonable manufacturing errors (element magnetization direction errors ≤5°), thus yielding practical designs to improve magnetic drug targeting treatment depths.     

Integrated experimental and computational approach for nanoparticle flow analysis

We report a new method combining computational fluid dynamics and flow experiments with customized channels to understand the transport of nanoparticles. Iron oxide nanoparticles, being highly attractive for biomedical research are chosen as model nanoparticles for the transport studies. Four different polyvinyl pyrrolidone and polyethyleneimine coated iron oxide nanoparticles of hydrodynamic sizes ranging from 45–178 nm were synthesized. These nanoparticles were adjusted to different target mass concentrations and ran through a bent tube to determine flow velocity and mass loss, specific to the nanoparticles. Computational predictions were made for velocity and mass loss of fully developed flow of nanoparticles through bent channel, which compared well with experimental measurements. A diffusion dominated nanoparticle flow is predicted, based on our results. This work will provide a breakthrough for further experimental and computational research to help understand the nanoparticle targeted delivery and the design of nanoparticles for optimal delivery in biomedical applications.