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 50mm 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 10%) could be retained at flow velocities up to 100 mm/s or to depths as far as 50mm 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 50mm inside the brain

Magnetic measurement methods to probe nanoparticle–matrix interactions

Magnetic nanoparticles (MNPs) are key elements in several biomedical applications, e.g., in cancer therapy. Here, the MNPs are remotely manipulated by magnetic fields from outside the body to deliver drugs or generate heat in tumor tissue. The efficiency and success of these approaches strongly depend on the spatial distribution and quantity of MNPs inside a body and interactions of the particles with the biological matrix. These include dynamic processes of the MNPs in the organism such as binding kinetics, cellular uptake, passage through cell barriers, heat induction and flow. While magnetic measurement methods have been applied so far to resolve the location and quantity of MNPs for therapy monitoring, these methods can be advanced to additionally access these particle–matrix interactions. By this, the MNPs can further be utilized as probes for the physical properties of their molecular environment. In this review, we first investigate the impact of nanoparticle–matrix interactions on magnetic measurements in selected experiments. With these results, we then advanced the imaging modalities magnetorelaxometry imaging and magnetic microsphere tracking to spatially resolve particle–matrix interactions

Magnetic measurement methods to probe nanoparticle–matrix interactions

Magnetic nanoparticles (MNPs) are key elements in several biomedical applications, e.g., in cancer therapy. Here, the MNPs are remotely manipulated by magnetic fields from outside the body to deliver drugs or generate heat in tumor tissue. The efficiency and success of these approaches strongly depend on the spatial distribution and quantity of MNPs inside a body and interactions of the particles with the biological matrix. These include dynamic processes of the MNPs in the organism such as binding kinetics, cellular uptake, passage through cell barriers, heat induction and flow. While magnetic measurement methods have been applied so far to resolve the location and quantity of MNPs for therapy monitoring, these methods can be advanced to additionally access these particle–matrix interactions. By this, the MNPs can further be utilized as probes for the physical properties of their molecular environment. In this review, we first investigate the impact of nanoparticle–matrix interactions on magnetic measurements in selected experiments. With these results, we then advanced the imaging modalities magnetorelaxometry imaging and magnetic microsphere tracking to spatially resolve particle–matrix interactions

Magnetically Responsive Microbubbles as Delivery Vehicles for Targeted Sonodynamic and Antimetabolite Therapy of Pancreatic Cancer

Magnetically responsive microbubbles (MagMBs), consisting of an oxygen gas core and a phospholipid coating functionalised with Rose Bengal (RB) and/or 5-fluorouracil (5-FU), were assessed as a delivery vehicle for the targeted treatment of pancreatic cancer using combined antimetabolite and sonodynamic therapy (SDT). MagMBs delivering the combined 5-FU/SDT treatment produced a reduction in cell viability of over 50% when tested against a panel of four pancreatic cancer cell lines in vitro. Intravenous administration of the MagMBs to mice bearing orthotopic human xenograft BxPC-3 tumours yielded a 48.3% reduction in tumour volume relative to an untreated control group (p<0.05) when the tumour was exposed to both external magnetic and ultrasound fields during administration of the MagMBs. In contrast, application of an external ultrasound field alone resulted in a 27% reduction in tumour volume. In addition, activated caspase and BAX protein levels were both observed to be significantly elevated in tumours harvested from animals treated with the MagMBs in the presence of magnetic and ultrasonic fields when compared to expression of those proteins in tumours from either the control or ultrasound field only groups (p<0.05). These results suggest MagMBs have considerable potential as a platform to enable the targeted delivery of combined sonodynamic / antimetabolite therapy in pancreatic cancer

Research data for: Optimized shapes of magnetic arrays for drug targeting applications

The .opj files can be opened using Origin (OriginLab, MA, USA). The file, "Volume dep study.opj" contains designs, data and analysis of optimized magnet arrays reported or referred to in the related publication, specifically in section 3.1. The file "POI dep study.opj" contains designs, data and analysis of optimized magnet arrays reported or referred to in the related publication, specifically in sections 3.2 and 3.5. The file "DOF dep study.opj" contains designs, data and analysis of optimized magnet arrays reported or referred to in the related publication, specifically in sections 3.3 and 3.6. The file "COMSOL particle trajectory simulations data and models.zip" is a compressed archive containing finite element model files, in .mph format, which can be opened using COMSOL Multiphysics (COMSOL, Inc, Burlington, MA, USA) and supporting look-up tables in spreadsheet format. The results generated from simulations using these model files are contained in the file "COMSOL particle tracing v2.opj", together with supporting data and analysis, following the methods outlined in sections 2.3 and 3.4 of the related publication

Research data for: Understanding the dynamics of superparamagnetic particles under the influence of high field gradient arrays

The archive file, "SW Experiments 170316.zip", contains all images obtained on 17 Mar 2016. Each file should involve images captured using a microscope of magnetic microbeads being conveyed in a glass capillary channel, focused into a single trajectory by a standing wave ultrasound field, and then magnetically deflected towards a magnet array, following the method described in the related publication. The .zip archive can be accessed along with all other parts ("SW Experiments 170316.z01" and "SW Experiments 170316.z02"), and the image files are organized inside the archive based on the nominal distance between the glass channel and magnet array, and labelled based on the experimental parameters set while the image was captured, including volumetric flow rate, run number and signal generator voltage. The .opj files can be opened using Origin (OriginLab, MA, USA). The file "Numerical simulations with linear Halbach Array.opj" contains data resulting from numerical simulations that are described and reported in section 3.1 of the related publication. The file "Numerical simulations with other magnetic systems.opj" contains data resulting from numerical simulations that are described and reported in section 3.3 of the related publication. The file "Magnetometry.opj" contains data resulting from magnetometry measurements of an ensemble of magnetic microbeads; the results are described and reported in appendix A of the related publication. The file "Analytical capture efficiencies with different initial distributions.opj" contains data resulting from semi-analytical simulations that are described and reported in appendix C of the related publication. The file, "Glass capillary device.mph" can be opened using COMSOL Multiphysics (COMSOL, Inc, Burlington, MA, USA) and contains a finite element model of the device used to generate an ultrasound standing wave inside a glass capillary channel. Results of simulations using this model are described and reported in appendix B of the related publication

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

The file, Magnetic_microbubble_retention_experiments_data.zip contains all videos obtained on 4 Dec 2014. Each video should involve magnetic targeting of microbubbles against flow. The Excel file in this compressed folder lists the type of magnet used during each video in terms of the time of day that the video was obtained. All other experimental parameters are detailed in the related publication. The .fig files, accessible using Matlab (MathWorks, Natick, MA, USA), display the regions of interest used to analyze each video and are named in terms of the time of day when the associated video was obtained. The .opj files can be opened using Origin (OriginLab, MA, USA), one of which stores analysis of results from the magnetic microbubble retention experiments and the other two give raw data and analysis of microbubble and ferrofluid magnetometry data obtained following the method described in the related publication. The Origin Graph file, Analysis_of_optimized_designs.opj contains designs, data and analysis of optimized magnet arrays reported or referred to in the related publication, as well as experimental Gaussmeter measurements of the assembled array, obtained following the methods described in the related publication. The COMSOL Model file, Assembled_array.mph can be opened using COMSOL Multiphysics (COMSOL, Inc, Burlington, MA, USA) and contains a finite element model of the assembled array reported in the related publication to model its magnetic properties.<br/

Research data for: Understanding the dynamics of superparamagnetic particles under the influence of high field gradient arrays

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Understanding the dynamics of superparamagnetic particles under the influence of high field gradient arrays

The aim of this study was to characterize the behaviour of superparamagnetic particles in magnetic drug targeting (MDT) schemes. A 3-dimensional mathematical model was developed, based on the analytical derivation of the trajectory of a magnetized particle suspended inside a fluid channel carrying laminar flow and in the vicinity of an external source of magnetic force. Semianalytical expressions to quantify the proportion of captured particles, and their relative accumulation (concentration) as a function of distance along the wall of the channel were also derived. These were expressed in terms of a non-dimensional ratio of the relevant physical and physiological parameters corresponding to a given MDT protocol.The ability of the analytical model to assess magnetic targeting schemes was tested against numerical simulations of particle trajectories. The semi-analytical expressions were found to provide good first-order approximations for the performance of MDT systems in which the magnetic force is relatively constant over a large spatial range. The numerical model was then used to test the suitability of a range of different designs of permanent magnet assemblies for MDT. The results indicated that magnetic arrays that emit a strong magnetic force that varies rapidly over a confined spatial range are the most suitable for concentrating magnetic particles in a localized region. By comparison, commonly used magnet geometries such as button magnets and linear Halbach arrays result in distributions of accumulated particles that are less efficient for delivery. The trajectories predicted by the numerical model were verified experimentally by acoustically focusing magnetic microbeads flowing in a glass capillary channel, and optically tracking their path past a high field gradient Halbach array