An Electromagnetic Steering System for Magnetic Nanoparticle Drug Delivery

Targeted delivery of pharmaceutical agents to the brain using magnetic nanoparticles (MNPs) is an efficient technique to transport molecules to disease locations. MNPs can cross the blood–brain barrier (BBB) and can be concentrated at a specific location in the brain using non-invasive electromagnetic forces. The proposed EMA consists of two coil-core system. The cores are added in the center of each coil to concentrate the flux in the region of interest. The EMA can enhance the gradient field 10 times compared to only coil system and generate the maximum magnetic field of 160 mT and 5.6 T/m. A 12-kW direct-current power supply was used to generate sufficient magnetic forces on the MNPs by regulating the input currents of the coils. Effective guidance of MNPs is demonstrated via simulations and experiments using 800-nm-diameter MNPs in a Y-shaped channel. The developed EMA system has high potentials to increase BBB crossing of MNPs for efficient drug targeting to brain region

Functionalized Magnetic Force Enhances Magnetic Nanoparticle Guidance: From Simulation to Crossing of the Blood-Brain Barrier in vivo

In recent studies, we introduced the concept of functionalized magnetic force as a method to prevent nanoparticles from sticking to vessel walls caused by extensive simulation and in vitro experiments involving a Y-shaped channel. In this study, we further investigated the effectiveness of the functionalized magnetic force with a realistic 3D vessel through simulations. For the simulations, we considered a more realistic continuous injection of particles with different magnetic forces and frequencies. Based on the results from our simulation studies, we performed in vivo mice experiments to evaluate the effectiveness of using a functionalized magnetic force to aid magnetic nanoparticles (MNPs) in crossing the blood-brain barrier (BBB). To implement the functionalized magnetic force, we developed an electromagnetic actuator regulated by a programmable direct current (DC) power supply. Our results indicate that a functionalized magnetic field can effectively prevent MNPs from sticking, and also guide them across the BBB. We used 770-nm fluorescent carboxyl MNPs in this study. Following intravenous administration of MNPs into mice, we applied an external magnetic field (EMF) to mediate transport of the MNPs across the BBB and into the brain. Furthermore, we evaluated the differential effects of functionalized magnetic fields (0.25, 0.5, and 1 Hz) and constant magnetic fields on the transport of MNPs across the BBB. Our results showed that a functionalized magnetic field is more effective than a constant magnetic field in the transport and uptake of MNPs across the BBB in mice. Specifically, applying a functionalized magnetic field with a 3 A current and 0.5 Hz frequency mediated the greatest transport and uptake of MNPs across the BBB in mic

Functionalized Magnetic Force Enhances Magnetic Nanoparticle Guidance: From Simulation to Crossing of the Blood-Brain Barrier in vivo

In recent studies, we introduced the concept of functionalized magnetic force as a method to prevent nanoparticles from sticking to vessel walls caused by extensive simulation and in vitro experiments involving a Y-shaped channel. In this study, we further investigated the effectiveness of the functionalized magnetic force with a realistic 3D vessel through simulations. For the simulations, we considered a more realistic continuous injection of particles with different magnetic forces and frequencies. Based on the results from our simulation studies, we performed in vivo mice experiments to evaluate the effectiveness of using a functionalized magnetic force to aid magnetic nanoparticles (MNPs) in crossing the blood-brain barrier (BBB). To implement the functionalized magnetic force, we developed an electromagnetic actuator regulated by a programmable direct current (DC) power supply. Our results indicate that a functionalized magnetic field can effectively prevent MNPs from sticking, and also guide them across the BBB. We used 770-nm fluorescent carboxyl MNPs in this study. Following intravenous administration of MNPs into mice, we applied an external magnetic field (EMF) to mediate transport of the MNPs across the BBB and into the brain. Furthermore, we evaluated the differential effects of functionalized magnetic fields (0.25, 0.5, and 1 Hz) and constant magnetic fields on the transport of MNPs across the BBB. Our results showed that a functionalized magnetic field is more effective than a constant magnetic field in the transport and uptake of MNPs across the BBB in mice. Specifically, applying a functionalized magnetic field with a 3 A current and 0.5 Hz frequency mediated the greatest transport and uptake of MNPs across the BBB in mic

Using Heparin-Coated Nanoparticles in the Treatment of Neointimal Hyperplasia

The use of stents in the treatment of atherosclerosis leads to a potential risk of restenosis, caused by neointimal hyperplasia. Neointimal hyperplasia is mainly caused by an injury to the endothelial layer of the blood vessel followed by the proliferation of smooth muscle cells into the lumen of the blood vessel. To address this, we designed a magnetically-guided drug delivery system to locally deliver heparin to a stented artery. The nanoparticles were synthesized, characterized, and tested on relevant human cell lines. The particles were non-toxic to human smooth muscle cells, endothelial cells, and fibroblasts. They reduced the proliferation of the smooth muscle cells and increased the proliferation of endothelial cells at concentrations as low as 10 μg/mL. The particles also shifted the smooth muscle cells from their synthetic phenotype to their contractile phenotype. The capture of the nanoparticles by the stent struts, under relevant magnetic field and blood velocity was modeled using COMSOL Multiphysics. The coronary artery was modeled using a 2D axisymmetric model with stainless steel stent struts. A Magnetic field of 1 T was applied to magnetize the stent struts. Three different strut geometries were compared for their effect of the capture efficiency. The model had a capture efficiency 0f 34-42%, which is comparable to models using the same particle sizes. Ex vivo organ culture studies using porcine right coronary arteries were performed. The arteries were conditioned either statically in cell culture flasks or dynamically in an organ culture bioreactor. Nanoparticles reduced intimal thickening in and expressed contractile properties in the treated arteries compared to the controls. We were successfully able to synthesize heparin-coated magnetic nanoparticles and achieve high heparin loading. Particle capture efficiency around the stent in the ex vivo porcine artery model was found to be similar to that predicted by the computational model. Consistent with the prior results of systemic heparin delivery, the nanoparticles reduce the proliferation and dedifferentiation of vascular smooth muscle cells while promoting endothelialization, both in vitro and ex vivo. Thus, these particles may be a promising treatment option for neointimal hyperplasia.

Channel Modeling for Diffusive Molecular Communication - A Tutorial Review

Molecular communication (MC) is a new communication engineering paradigm where molecules are employed as information carriers. MC systems are expected to enable new revolutionary applications such as sensing of target substances in biotechnology, smart drug delivery in medicine, and monitoring of oil pipelines or chemical reactors in industrial settings. As for any other kind of communication, simple yet sufficiently accurate channel models are needed for the design, analysis, and efficient operation of MC systems. In this paper, we provide a tutorial review on mathematical channel modeling for diffusive MC systems. The considered end-to-end MC channel models incorporate the effects of the release mechanism, the MC environment, and the reception mechanism on the observed information molecules. Thereby, the various existing models for the different components of an MC system are presented under a common framework and the underlying biological, chemical, and physical phenomena are discussed. Deterministic models characterizing the expected number of molecules observed at the receiver and statistical models characterizing the actual number of observed molecules are developed. In addition, we provide channel models for time-varying MC systems with moving transmitters and receivers, which are relevant for advanced applications such as smart drug delivery with mobile nanomachines. For complex scenarios, where simple MC channel models cannot be obtained from first principles, we investigate simulation-driven and experimentally-driven channel models. Finally, we provide a detailed discussion of potential challenges, open research problems, and future directions in channel modeling for diffusive MC systems.Comment: 40 pages; 23 figures, 2 tables; this paper is submitted to the Proceedings of IEE

Channel modeling for diffusive molecular communication - a tutorial review

Molecular communication (MC) is a new communication engineering paradigm where molecules are employed as information carriers. MC systems are expected to enable new revolutionary applications such as sensing of target substances in biotechnology, smart drug delivery in medicine, and monitoring of oil pipelines or chemical reactors in industrial settings. As for any other kind of communication, simple yet sufficiently accurate channel models are needed for the design, analysis, and efficient operation of MC systems. In this paper, we provide a tutorial review on mathematical channel modeling for diffusive MC systems. The considered end-to-end MC channel models incorporate the effects of the release mechanism, the MC environment, and the reception mechanism on the observed information molecules. Thereby, the various existing models for the different components of an MC system are presented under a common framework and the underlying biological, chemical, and physical phenomena are discussed. Deterministic models characterizing the expected number of molecules observed at the receiver and statistical models characterizing the actual number of observed molecules are developed. In addition, we provide channel models for timevarying MC systems with moving transmitters and receivers, which are relevant for advanced applications such as smart drug delivery with mobile nanomachines. For complex scenarios, where simple MC channel models cannot be obtained from first principles, we investigate simulation-driven and experiment-driven channel models. Finally, we provide a detailed discussion of potential challenges, open research problems, and future directions in channel modeling for diffusive MC systems

Synthesis, Biofunctionalization, and Application of Magnetic Nanomaterials

Since their inception in the late 1970\u27s magnetic nanomaterials have sparked heavy research into their use in the biomedical field. Their unique magnetic properties allow the magnetic particles to be the base for a large array of expiremental medical techniques, from treatments of disease, diagnostic tests, imaging aids, and more. In this manuscript, each stage starting from novel particle synthesis, functionalization with bioactive molecules, and innovative application is explored, specifically using the techniques magnetically mediated energy delivery, magnetophoresis, magnetic resonance imaging. The reproducible synthesis of nanomaterials is necessary if any further engineering application is going to be done. Using a novel extended LaMer approach where a precursor solution is consistently added to a reaction vessel allows for the linear volume growth of nanoparticles. This technique was originally used for the synthesis of magnetite (a simple ferrite) to control the volume of the particle indefinitely. Transferring it to a nonstoichiometric cobalt ferrite, it is shown that a linear volume growth is achieved up to 20nm. Secondary functionality of the magnetic particles has really opened up the application to sensing, selective treatment, and functional imaging. Surface modification with a bacterial strain discriminatory glycan allows for strain selective treatment of bacterial infection. Heparin functional particles show high pharmacokinetic activity for the treatment of neointimal hyperplasia due to high surface area to volume ratios. Gadolinium coated particles have distance dependent effects on the MRI relaxation rate of water, which may prove useful in functional imaging. Each of these complexes shows promise as a new way to treat or image malady. Although a small part in the large picture in developing a new generation of medicine, this research lays the foundation for each of these possible treatments. Be it the eradication of bacterial infection or the non-toxic prevention of restenosis, novel multifunctional nanomaterials such as the ones discussed in this manuscript, will be heavily relied on in the future of medicine