Magnetic Drug Targeting Applications Research Articles

Pulsatile blood flow simulations of magnetic drug targeting (MDT) for drug particles dispersion through stenosis asymmetric and symmetric vessels

Magnetic drug delivery has emerged as an innovative strategy for addressing medical conditions like tumors and vascular occlusions. In this study, we delve into the influence of magnetic fields on three-dimensional models representing various vessel configurations, including unobstructed, asymmetric, and symmetric vessels. We take into account critical factors such as non-Newtonian viscosity, pulsatile flow, and the presence of vessel obstructions. By investigating drug particles ranging from 1 to 4 µm in diameter, our findings illuminate the central role that magnetic particles play in Magnetic Drug Targeting (MDT). Importantly, we observe a substantial enhancement in drug particle capture efficiency in the presence of a magnetic field, particularly for larger particle diameters. Nevertheless, this efficiency saturates at 100% for diameters exceeding 3 µm due to particle–wall interactions. Interestingly, within potential obstruction areas, particle capture efficiency exhibits a nuanced relationship with diameter. Even at a diameter of 4 µm, the magnetic field's influence on vessel walls leads to particle capture before reaching obstructions, thus reducing efficiency. Comparing scenarios without a magnetic field, it is found that symmetrical obstructions yield higher capture efficiency compared to asymmetrical vessels, and asymmetric vessels outperform their smoother counterparts. Moreover, the presence of vessel obstructions amplifies drug particle capture efficiency. Consequently, our simulations unveil significant potential for the application of MDT in the treatment of atherosclerosis. From a physics perspective, these results offer promising prospects for the application of Magnetic Drug Targeting in the realm of cardiovascular diseases.

Synthesis of Poly(2-Hydroxyethyl Methacrylate) (PHEMA)-Based Superparamagnetic Nanoparticles for Biomedical and Pharmaceutical Applications.

The performance of polymeric nanomaterials relies greatly upon their properties which are intimately related to the methods of fabrication of their materials. Among various synthetic polymers the polymers of 2-hydroxyethyl methacrylate (PHEMA) maintains a prime position in the biomedical field due to their useful physicochemical properties and suitability for controlled drug delivery applications. Furthermore, the addition of iron oxide to PHEMA nanoparticles imparts superparamagnetism to the nanoparticles and expands the range of their uses to include magnetic drug targeting applications. Here we focus on three methods for preparation of PHEMA nanoparticles, one by suspension polymerization, a second by emulsion polymerization without the use of any surfactants, and the final one with the incorporation of iron oxide into PHEMA nanoparticles.

Facile synthesis and characterization of iron oxide–egg albumin (IOEA) as core–shell nanoparticles and study of water intake potential

In the present study an in-situ chemical precipitation method was followed to design core–shell nanoparticles having iron oxide as the core and glutaraldehyde-crosslinked egg albumin as shell. The experimental conditions like the concentrations of Fe2+/Fe3+ ions, egg albumin, and glutaraldehyde, pH and temperature were optimized to achieve controllable and desired size of nanoparticles suitable for magnetic drug targeting applications. The nanoparticles were characterized by FTIR, XRD, TEM, DSC, DLS and surface charge measurements techniques. The prepared core–shell nanoparticles were also studied by vibrating sample magnetometer (VSM) method to seek information about their superparamagnetic nature. The suitability of nanoparticles to function as swelling controlled drug delivery system was also examined by conducting swelling experiments in PBS (pH 7.4) under varying experimental conditions and the results obtained were optimized to achieve the conditions at which an optimum swelling behavior was obtained.

Optimized shapes of magnetic arrays for drug targeting applications

Arrays of permanent magnet elements have been utilized as light-weight, inexpensive sources for applying external magnetic fields in magnetic drug targeting applications, but they are extremely limited in the range of depths over which they can apply useful magnetic forces. In this paper, designs for optimized magnet arrays are presented, which were generated using an optimization routine to maximize the magnetic force available from an arbitrary arrangement of magnetized elements, depending on a set of design parameters including the depth of targeting (up to 50 mm from the magnet) and direction of force required. A method for assembling arrays in practice is considered, quantifying the difficulty of assembly and suggesting a means for easing this difficulty without a significant compromise to the applied field or force. Finite element simulations of in vitro magnetic retention experiments were run to demonstrate the capability of a subset of arrays to retain magnetic microparticles against flow. The results suggest that, depending on the choice of array, a useful proportion of particles (more than ) could be retained at flow velocities up to 100 mm s−1 or to depths as far as 50 mm from the magnet. Finally, the optimization routine was used to generate a design for a Halbach array optimized to deliver magnetic force to a depth of 50 mm inside the brain.

Nanomedical innovation: the SEON-concept for an improved cancer therapy with magnetic nanoparticles.

Nanomedicine offers tremendous opportunities for the development of novel therapeutic and diagnostic tools. During the last decades, extensive knowledge was gained about stabilizing and the coating of nanoparticles, their functionalization for drug binding and drug release and possible strategies for therapies and diagnostics of different diseases. Most recently, more and more emphasis has been placed on nanotoxicology and nanosafety aspects. The section of experimental oncology and nanomedicine developed a concept for translating this knowledge into clinical application of magnetic drug targeting for the treatment of cancer and other diseases using superparamagnetic iron oxide nanoparticles. This approach includes reproducible synthesis, detailed characterization, nanotoxicological testing, evaluation in ex vivo models, preclinical animal studies and production of superparamagnetic iron oxide nanoparticles according to good manufacturing practice regulations.

Halbach arrays consisting of cubic elements optimised for high field gradients in magnetic drug targeting applications

A key challenge in the development of magnetic drug targeting (MDT) as a clinically relevant technique is designing systems that can apply sufficient magnetic force to actuate magnetic drug carriers at useful tissue depths. In this study an optimisation routine was developed to generate designs of Halbach arrays consisting of multiple layers of high grade, cubic, permanent magnet elements, configured to deliver the maximum pull or push force at a position of interest between 5 and 50 mm from the array, resulting in arrays capable of delivering useful magnetic forces to depths past 20 mm. The optimisation routine utilises a numerical model of the magnetic field and force generated by an arbitrary configuration of magnetic elements. Simulated field and force profiles of optimised arrays were evaluated, also taking into account the forces required for assembling the array in practice. The resultant selection for the array, consisting of two layers, was then constructed and characterised to verify the simulations. Finally the array was utilised in a set of in vitro experiments to demonstrate its capacity to separate and retain microbubbles loaded with magnetic nanoparticles against a constant flow. The optimised designs are presented as light-weight, inexpensive options for applying high-gradient, external magnetic fields in MDT applications.

Rhodamine-loaded, cross-linked, carboxymethyl cellulose sodium-coated super-paramagnetic iron oxide nanoparticles: Development and in vitro localization study for magnetic drug-targeting applications

Abstract A facile, one-pot, room-temperature synthesis method for super-paramagnetic iron oxide nanoparticles (SPIONs) employing simple reactants was attempted using a battery of stabilizers possessing either hydroxyl (methyl cellulose, polyethylene glycol), or a combination of hydroxyl and carboxyl functional groups (carboxymethyl cellulose sodium, trisodium citrate, α-tocopheryl polyethylene glycol succinate), from carbohydrate and non-carbohydrate sources, added to the reaction mixture in situ. Finally, carboxymethyl cellulose sodium (CMC)-coated SPIONs were selected, which were further cross-linked with epichlorohydrin to improve the stability of coating and load a water-soluble model molecule, rhodamine B. The selected formulation with optimum nanometric size (24 ± 8 nm) was characterized for morphology, surface charge, interaction of CMC with iron oxide, crystal phase, magnetization properties and finally microfluidic studies were carried out on the optimized formulation to determine the in vitro SPIONs localization pattern in the presence of an external magnetic field (150 mT) in a simulated glass capillary to demonstrate its targeting potential. A biconvex pattern of aggregation was observed when observed for time, t = 0–100 s with the rate of localization decreasing as a function of time. The study was used to standardize CMC as a standard capping agent for the formulation of SPIONs, which have potential for numerous bio-medical applications, and to load rhodamine B as a water-soluble model molecule.

On Computational Fluid Dynamics Study of Magnetic Drug Targeting

Magnetic drug targeting is continuing to draw attention as a potential technique for cancer and tumour treatment. This paper focuses on the development of computational fluid dynamic models for magnetic drug targeting. Magnetic particle capture has been simulated in a 90o coronary artery bend of circular tube for a range of different particle sizes. The magnetic field is produced by a current carrying wire. It has been found that increasing the sizes of magnetic particles increases the capture of particles. Extensions are made on the model to include the effects of non-Newtonian fluid and the pulsating nature of blood flow. These extensions improved the basic model by simulating a more physiologically accurate application of magnetic drug targeting. A reduction of the particle capture efficiency is experienced based on this physiologically accurate model. Time of injection over the flow cycle of the pulsating nature of blood flow greatly influences the particle capture efficiency.

Mathematical modelling for trajectories of magnetic nanoparticles in a blood vessel under magnetic field

Abstract A mathematical model is developed to describe the trajectories of a cluster of magnetic nanoparticles in a blood vessel for the application of magnetic drug targeting (MDT). The magnetic nanoparticles are injected into a blood vessel upstream from a malignant tissue and are captured at the tumour site with help of an applied magnetic field. The applied field is produced by a rare earth cylindrical magnet positioned outside the body. All forces expected to significantly affect the transport of nanoparticles were incorporated, including magnetization force, drag force and buoyancy force. The results show that particles are slow down and captured under the influence of magnetic force, which is responsible to attract the magnetic particles towards the magnet. It is optimized that all particles are captured either before or at the centre of the magnet (z≤0) when blood vessel is very close proximity to the magnet (d=2.5 cm). However, as the distance between blood vessel and magnet (d) increases (above 4.5 cm), the magnetic nanoparticles particles become free and they flow away down the blood vessel. Further, the present model results are validated by the simulations performed using the finite element based COMSOL software.

Simulation of Magnetic Nanoparticles in Blood Flow for Magnetic Drug Targeting Applications

Article Simulation of Magnetic Nanoparticles in Blood Flow for Magnetic Drug Targeting Applications was published on September 7, 2013 in the journal Biomedical Engineering / Biomedizinische Technik (volume 58, issue SI-1-Track-B).

Magnetically induced phase condensation in an aqueous dispersion of magnetic nanogels

The applicability of aqueous magnetic colloids depends on their colloidal stability under the influence of various factors like external magnetic field and temperature. The magnetically induced phase condensation of magnetic colloids leads to the formation of spindle-like condensed phase drops of highly packed magnetic colloidal particles. The condensed phase drops are aligned parallel to the external magnetic field and may grow up to several microns thickness and tens or even hundreds of microns length. Thus, the magnetically induced phase condensation could be an advantage in magnetic separation applications, whereas in magnetic drug targeting applications it could lead to blood vessel clogging as well as to a significant decrease of the specific surface. We present the results of an experimental study regarding the influence of the external magnetic field and temperature on the magnetically induced phase condensation in an aqueous dispersion of pNIPA magnetic nanogels. A theoretical model was developed for the analysis of the data from forward light scattering experiments. It was found that the volume weight of the condensed phase increases with passing time, with increasing field intensity and temperature decrease. Using the proposed model, the magnetic field intensity dependence of the initial supersaturation of the sample was calculated.

Numerical Simulations of Ferrofluids for Magnetic Drug Targeting Applications

Numerical Simulations of Ferrofluids for Magnetic Drug Targeting Applications

Pegylated magnetic nanocarriers for doxorubicin delivery: A quantitative determination of stealthiness in vitro and in vivo

The aim of this work was to elucidate the impact of polyethylene glycol (PEG) polymeric coating on the in vitro and in vivo stealthiness of magnetic nanocarriers loaded or not with the anticancer drug doxorubicin. The comparison was made between aqueous suspensions of superparamagnetic iron oxide nanoparticles (SPIONs) stabilized by either citrate ions (C-SPIONs) or PEG5000 (P-SPIONs), the latter being loaded or not with doxorubicin via the formation of a DOX-Fe2+ complex (DLP-SPIONs).After determination of their relevant physico-chemical properties (size and surface charge), nanoparticle (NP) stealthiness was studied in vitro (ability to activate the complement system and uptake by monocytes and macrophage-like cells) and in vivo in mice (blood half-life; t1/2, and biodistribution in main clearance organs). These aspects were quantitatively assessed by atomic absorption spectrometry (AAS). Complement activation dramatically decreased for sterically stabilized P-SPIONs and DLP-SPIONs in comparison with C-SPIONs stabilized by charge repulsion. Monocyte and macrophage uptake was also largely reduced for pegylated formulations loaded or not with doxorubicin. The t1/2 in blood for P-SPIONs was estimated to be 76±6min, with an elimination mainly directed to liver and spleen. Thanks to their small size (<80nm) and a neutral hydrophilic polymer-extended surface, P-SPIONs exhibit prolonged blood circulation and thus potentially an increased level in tumor delivery suitable for magnetic drug targeting applications.

Analyzing ferrofluid transport for magnetic drug targeting

Experimental and numerical investigations of magnetically induced localization of ferrofluid and its subsequent dispersion are performed in a forced flow. The ferrofluid accumulation behaves as a solid obstacle in the flow as the competing magnetic and fluid shear forces give rise to a rigidly bound core region followed by a washaway region at its wake. Results of the analysis provide meaningful information on ferrofluid transport for various magnetic drug targeting applications.