Implant assisted-magnetic drug targeting: Comparison of in vitro experiments with theory

Implant assisted-magnetic drug targeting (IA-MDT) was studied both in vitro and theoretically, with extensive comparisons made between model and experiment. Magnetic drug carrier particles (MDCPs) comprised of magnetite encased in a polymer were collected magnetically using a ferromagnetic, coiled, wire stent as the implant and a NdFeB permanent magnet for the applied magnetic field. A 2-D mathematical model with no adjustable parameters was developed and compared to the 3-D experimental results. The effects of the fluid velocity, stent and MDCP properties, and magnetic field strength on the performance of the system were evaluated in terms of the capture efficiency (CE) of the MDCPs. In nearly all cases, the parametric trends predicted by the model were in good agreement with the experimental results: the CE always increased with decreasing velocity, increasing magnetic field strength, increasing MDCP size or magnetite content, or increasing wire size. The only exception was when experiments showed an increase in the CE with an increase in the number of loops in the wire, while the model showed no dependence. The discrepancies between experiment and theory were attributed to phenomena not accounted for by the model, such as 3-D to 2-D geometric and magnetic field orientation differences, and interparticle interactions between the MDCPs that lead to magnetic agglomeration and shearing force effects. Overall, this work showed the effectiveness of a stent-based IA-MDT system through both in vitro experimentation and corroborated theory, with the designs of the ferromagnetic wire and the MDCPs both being paramount to the CE.     

In vitro study of ferromagnetic stents for implant assisted-magnetic drug targeting

Implant-assisted-magnetic drug targeting (IA-MDT) was studied in vitro using a coiled ferromagnetic wire stent made from stainless steel 430 or 304, and magnetic drug carrier particle (MDCP) surrogates composed of poly(styrene/divinylbenzene) embedded with 20 wt% magnetite. The fluid velocity, particle concentration, magnetic field strength, and stent material all proved to be important for capturing the MDCP surrogates. Overall, this in vitro study further confirmed the important role of the ferromagnetic implant for attracting and retaining MDCPs at the target zone.     

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.     

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.     

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.     

Analysis of magnetic drug carrier particle capture by a magnetizable intravascular stent—2: Parametric study with multi-wire two-dimensional model

A 2-D mathematical model was developed and used to examine the capture of magnetic drug carrier particles (MDCPs) by a magnetizable intravascular stent (MIS). The roles of both non-stent system parameters, i.e., the blood flow rate, magnetic field strength and direction and MDCP properties, and stent design parameters, i.e., the MIS radius, its wire radius, number of MIS loops, interwire loop spacing and MIS ferromagnetic material were evaluated over a wide range of plausible conditions. The results showed that the MIS could be a very effective magnetic drug targeting tool with many possible applications.     

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.     

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.     

In-plane magnetic pattern separation in NiFe/NiO and Co/NiO exchange biased bilayers investigated by magnetic force microscopy

Ion bombardment induced magnetic patterning (IBMP) was used to write in-plane magnetized micro and submicron patterns in exchange biased magnetic bilayers, where the magnetization directions of the adjacent patterns are antiparallel to each other in remanence. These magnetic patterns were investigated by non-contact magnetic force microscopy (MFM). It is shown that the recorded MFM images of the IBMP patterns in two exemplarily chosen standard layer systems (NiFe (4.8 nm)/NiO (68 nm) and Co (4.8 nm)/NiO (68 nm)) can be well described by a model within the point-dipole approximation for the tip magnetization. For 5 and 0.9 μm wide bar patterns the domain wall widths between adjacent magnetically patterned areas were determined to a≈1 μm. The minimum magnetically stable pattern width was estimated to be 0.7 μm in the standard system Co (4.8 nm)/NiO (68 nm).     

Ferromagnetic seeding for the magnetic targeting of drugs and radiation in capillary beds

A new implant assisted-magnetic drug targeting approach is introduced and theoretically analyzed to demonstrate its feasibility. This approach uses ferromagnetic particles as seeds for collecting magnetic drug carrier particles at the desired site in the body, such as in a capillary bed near a tumor. Based on the capture cross section (λ_c) approach, a parametric study was carried out using a 2-D mathematical model to reveal the effects of the magnetic field strength (μ₀H₀=0.01–1.0 T), magnetic drug carrier particle radius (R_p=20–500 nm), magnetic drug carrier particle ferromagnetic material content (x_fm,p=20–80 wt%), average blood velocity (u_B=0.05–1.0 cm/s), seed radius (R_s=100–2000 nm), number of seeds (N_s=1–8), seed separation (h=0–8R_s), and magnetic drug carrier particle and seed ferromagnetic material saturation magnetizations (iron, SS 409, magnetite, and SS 304) on the performance of the system. Increasing the magnetic field strength, magnetic drug carrier particle size, seed size, magnetic drug carrier particle ferromagnetic material content, or magnetic drug carrier particle or seed saturation magnetization, all positively and significantly affected λ_c, while increasing the average blood velocity adversely affected it. Increasing the number of seeds or decreasing the seed separation, with both causing less significant increases in λ_c, verified that cooperative magnetic effects exist between the seeds that enhance the performance. Overall, these theoretical results were encouraging as they showed the viability of this minimally invasive, implant assisted-magnetic drug targeting approach for targeting drugs or radiation in capillary beds.     

Many particle magnetic dipole-dipole and hydrodynamic interactions in magnetizable stent assisted magnetic drug targeting

The implant assisted magnetic targeted drug delivery system of Avilés, Ebner and Ritter is considered both experimentally (in vitro) and theoretically. The results of a 2D mathematical model are compared with 3D experimental results for a magnetizable wire stent. In this experiment a ferromagnetic, coiled wire stent is implanted to aid collection of particles which consist of single domain magnetic nanoparticles (radius ). In order to model the agglomeration of particles known to occur in this system, the magnetic dipole-dipole and hydrodynamic interactions for multiple particles are included. Simulations based on this mathematical model were performed using open source C++ code. Different initial positions are considered and the system performance is assessed in terms of collection efficiency. The results of this model show closer agreement with the measured in vitro experimental results and with the literature. The implications in nanotechnology and nanomedicine are based on the prediction of the particle efficiency, in conjunction with the magnetizable stent, for targeted drug delivery.     

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     

The order of magnetic phase transition in La(Fe1−xCox)11.4Si1.6 compounds

Magnetic transitions in La(Fe_1−xCo_x)_11.4Si_1.6 compounds with x=0–0.08, have been studied by DC magnetic measurements and Mössbauer spectroscopy. The temperature dependence of the Landau coefficients has been derived by fitting the magnetization, M(μ₀H), using the Landau expansion of the magnetic free energy. For x0.02 there is a strongly first-order magnetic phase transition between ferromagnetic and paramagnetic (F–P) states in zero external field and a metamagnetic transition from paramagnetic to ferromagnetic (P–F) above T_c. Increasing the cobalt content drives the F–P transition towards second order and eliminates the metamagnetic transition.     

Magnetic properties of Fe-based glass-coated microwires

Axial hysteresis loops of glass-coated amorphous Fe₇₀B₁₅Si₁₀C₅ microwire have been measured as a function of both the diameter of metallic nucleus (from 3.7–14.9 μm) and the thickness of the coating (4.0–9.6 μm). They exhibit low-field rectangular hysteresis loops with a single and large Barkhausen jump even for samples as short as 5 mm long. Coercivity remarkably increases (roughly from 1 to 10 Oe) and remanence decreases (from 1 to 0.45 T), respectively, as the ratio of metallic nucleus radius to the total radius of the wire decreases from 0.63 to 0.16. The strength of the internal stresses induced during the fabrication depends on this ratio, and the easy axes of the corresponding magnetoelastic anisotropies determine the actual value of coercivity and remanence for these microwires.     

Study of fast switching processes due to electric and magnetic fields-an NMR approach

Solid state NMR techniques have been developed to investigate dynamic molecular effects (e.g., molecular reorientations) due to simultaneously applied external electric fields on electrically sensitive materials such as liquid crystals (LC), liquid crystalline polymers (LCP) and polymeric electrets. Such effects can be observed only on relatively thin systems (10-200 μm). That means that many scans are necessary to achieve a sufficiently high signal-to-noise-ratio in the spectra (500-1000 scans). If the material is also magnetically sensitive, the electric field can be used to orient molecules in a starting orientational state and by switching-off the voltage to access fast reorientation processes in the magnetic field B₀. Until now, the behaviour of orientable molecular systems under the influence of electric fields has been investigated by means of a more or less quasistatic approach (LCP: 100 V, electrets: 1 kV) in equilibrium states. The achievable time resolution depends on the desired signal-to-noise-ratio. For the case of proton NMR this means a time resolution of about 10 min. However, very often switching processes occur on a much shorter time scale. Using conventional techniques it is impossible to observe fast (ca. 100 μs) electrically or magnetically induced reorientation processes. In this work, we present a concept to overcome the problems outlined above and to extend the area of our current in situ NMR investigations on thin electrically-switched or poled polymeric layers. The basic idea is to include synchronized electric pulses during the NMR experiment using the preparation and/or mixing periods of a 1D or 2D pulse sequence for the application of an orienting field (electric or magnetic) and to use the reversibility of the molecular switching phenomenon to achieve a sufficient signal-to-noise-ratio. The techniques extend the range of possible investigations from about 100 μs to approximately T₁ for correlated spectra (and to longer times of applied fields for uncorrelated spectra). Results are shown for a nematic LC and a nematic polymer having a similar side chain.     

Inclusion of magnetic dipole-dipole and hydrodynamic interactions in implant-assisted magnetic drug targeting

Mathematical modelling of the implant-assisted magnetic drug targeting system of Avilés, Ebner and Ritter is performed. In order to model the agglomeration of particles known to occur in this system, the magnetic dipole-dipole and hydrodynamic interactions are included. Such interactions were calculated previously by Mikkelsen et al. under low magnetic fields (~0.05 T) in microfluidic systems. Here, a higher magnetic field (0.7 T) is considered and the effect of interactions on two nanoparticles with a seed implant is calculated. The calculations were performed with the open-source software OpenFOAM. Different initial positions are considered and the system performance is assessed in terms of capture cross section. Inclusion of both interactions was seen to alter the capture cross section of the system by up to 7% in absolute terms.     

Low frequency magnetic noise in epitaxial antiferromagnetically coupled Fe/Cr multilayers

For antiferromagnetically coupled epitaxial [Fe/Cr(001)]₁₀ multilayers we detected a strong enhancement of the magnetism-related electrical noise in the vicinity of the orientation transition between the easy and hard axes. Our measurements are performed at different temperatures and we also identified the noise caused by depinning of domain walls (DWs). We are able to detect and follow in real time the motion of rather extended (of the order of 100 μm) DWs by comparing the magnetic noise in the presence and absence of a DC transport current, respectively. The presence of large and small (<1 μm) DWs is confirmed by magnetic force microscopy images obtained at room temperature.     

Tight-binding study of ammonia and hydrogen adsorption on magnetic cobalt systems

The semi-empirical self-consistent tight-binding model of ammonia and hydrogen adsorption at Co(0001) and small Co clusters is used to study the chemisorption role in surface magnetism. The adsorbate choice has been suggested by recent experiments. At the Co(0001) surface the atomic magnetization is predicted to diminish locally by 0.26 μ_B due to an isolated hydrogen atom adsorption; for Co₁₃ clusters the change is somewhat smaller but less localized. At H(1×1)–Co(0001) the magnetization of surface Co atoms drops to 0.88 μ_B. The hydrogen magnetic moment is very small and couples antiferromagnetically to Co. Ammonia adsorption is found to reduce the Co atom magnetization locally by 0.1 μ_B or less. We discuss the possibility of adsorbate–metal antiferromagnetic coupling in more detail.     

Surface barrier and magnetic hysteresis of ac permeability in YBaCuO single crystal

The nature of hysteretic behavior of the flux line lattice (FLL) contribution to ac magnetic permeability (μ_v) is analyzed for the case of YBa₂Cu₃O_x single crystal (at applied magnetic field Hc axis). It is shown that hysteresis loops μ_v(H) corresponding to different temperatures (T=70–84 K) are scaled to a universal curve in normalized coordinates. Such a behavior is interpreted in terms of the FLL interaction with the crystal surface. The explicit relationship between μ_v and magnetic induction B is found for the near-surface region of the superconductor. It is shown that the μ_v(H) loops are closely related to the hysteresis of B at cycling of applied magnetic field. The latter hysteresis stems from the Bean–Livingston surface barrier. The estimates demonstrate strong suppression of the surface barrier in YBa₂Cu₃O_x crystal in comparison to that expected for the ideal surface. As a result, the lower branch of the hysteresis loop corresponding to the increasing field is very close to the equilibrium μ_v(H) curve and the surface barrier appreciably affects only the upper branch when magnetic flux leaves the sample. The comparison of theoretical predictions and experimental data provides an opportunity to refine the actual range of stability H_max(B)–H_min(B) for the FLL at fixed B for YBa₂Cu₃O_x crystal in the case of Hc.     

Origin of ferromagnetism and nano-scale phase separations in diluted magnetic semiconductors

This paper reviews various origins of ferromagnetic response that has been detected in diluted magnetic semiconductors (DMS). Particular attention is paid to those ferromagnetic DMS in which no precipitation of other crystallographic phases has been observed. It is argued that these materials can be divided into three categories. The first consists of (Ga,Mn)As and related compounds. In these solid solutions the theory built on p–d Zener's model of hole-mediated ferromagnetism and the Kohn–Luttinger kp theory of semiconductors describes quantitatively thermodynamic, micromagnetic, optical, and transport properties. Moreover, the understanding of these materials has provided a basis for the development of novel methods enabling magnetisation manipulation and switching. To the second group belong compounds, in which a competition between long-range ferromagnetic and short-range antiferromagnetic interactions and/or the proximity of the localisation boundary lead to an electronic nano-scale phase separation that results in characteristics similar to colossal magnetoresistance oxides. Finally, in a number of compounds a chemical nano-scale phase separation into the regions with small and large concentrations of the magnetic constituent is present. It has recently been suggested that this spinodal decomposition can be controlled by the charge state of relevant magnetic impurities. This constitutes a new perspective method for 3D self-organised growth of coherent magnetic nanocrystals embedded by the semiconductor matrix.