Simulation of Enhanced Deposition Due to Magnetic Field Alignment of Ellipsoidal Particles in a Lung Bifurcation

Martinez, Roberto; Roshchenko, Andriy; Minev, Peter; Finlay, Warren H.

doi:10.1089/jamp.2011.0921

Cited by 8 publications

(3 citation statements)

References 37 publications

(100 reference statements)

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“…The experimental results were found to be in good agreement with the CFD simulation data. In another study, Martinez et al [ 224 ] developed a CFD model to study drug delivery through deep down airways by ellipsoidal magnetic particles, where the results showed that the presence of the magnetic increases local enhancement in drug delivery by a factor of 1.43–3.46 in symmetrical bronchial bifurcation. Pourmehran et al [ 225 ] presented a CFD model of a realistic lung model (G0-G2) to investigate deposition efficiency under the influence of non-uniform magnetic field.…”

Section: Magnetic Drug Delivery To Lung Tumors Through the Respiratormentioning

confidence: 99%

Magnetic particle targeting for diagnosis and therapy of lung cancers

Saadat

Manshadi

Mohammadi

et al. 2020

Journal of Controlled Release

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Over the past decade, the growing interest in targeted lung cancer therapy has guided researchers toward the cutting edge of controlled drug delivery, particularly magnetic particle targeting. Targeting of tissues by magnetic particles has tackled several limitations of traditional drug delivery methods for both cancer detection (e.g., using magnetic resonance imaging) and therapy. Delivery of magnetic particles offers the key advantage of high efficiency in the local deposition of drugs in the target tissue with the least harmful effect on other healthy tissues. This review first overviews clinical aspects of lung morphology and pathogenesis as well as clinical features of lung cancer. It is followed by reviewing the advances in using magnetic particles for diagnosis and therapy of lung cancers: (i) a combination of magnetic particle targeting with MRI imaging for diagnosis and screening of lung cancers, (ii) magnetic drug targeting (MDT) through either intravenous injection and pulmonary delivery for lung cancer therapy, and (iii) computational simulations that models new and effective approaches for magnetic particle drug delivery to the lung, all supporting improved lung cancer treatment. The review further discusses future opportunities to improve the clinical performance of MDT for diagnosis and treatment of lung cancer and highlights clinical therapy application of the MDT as a new horizon to cure with minimal side effects a wide variety of lung diseases and possibly other acute respiratory syndromes (COVID-19, MERS, and SARS).

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Section: Magnetic Drug Delivery To Lung Tumors Through the Respiratormentioning

confidence: 99%

Magnetic particle targeting for diagnosis and therapy of lung cancers

Saadat

Manshadi

Mohammadi

et al. 2020

Journal of Controlled Release

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“…It has been hypothesized that some of these drawbacks could be alleviated through the incorporation of magnetic agents into the inhalable drugs and thereby control lung deposition using external magnetic fields (Christian, 2008;Longest and Holbrook, 2012;Saadat et al, 2020); a concept that has been extensively explored in silico over the past decade with computational fluid dynamic simulations (Kenjereš and Tjin, 2017;Manshadi et al, 2019;Martinez et al, 2012;Pourmehran et al, 2015). Since the aerodynamic drag forces exerted on airborne inhaled particles are vastly stronger than the magnetic force imposed by magnets, deflecting particles under airflow and depositing them on target has been limited.…”

Section: Introductionmentioning

confidence: 99%

Focused targeting of inhaled magnetic aerosols in reconstructed in vitro airway models

Ostrovski

Dorfman

Poh

et al. 2021

Journal of Biomechanics

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The pulmonary tract is an attractive route for topical treatments of lung diseases. Yet, our ability to confine the deposition of inhalation aerosols to specific lung regions, or local airways, remains still widely beyond reach. It has been hypothesized that by coupling magnetic particles to inhaled therapeutics the ability to locally target airway sites can be substantially improved. Although the underlying principle has shown promise in seminal in vivo animal experiments as well as in vitro and in silico studies, its practical implementation has come short of delivering efficient localized airway targeting. Here, we demonstrate in an in vitro proof-of-concept an inhalation framework to leverage magnetically-loaded aerosols for airway targeting in the presence of an external magnetic field. By coupling the delivery of a short pulsed bolus of sub-micron (~500 nm diameter) droplet aerosols with a custom ventilation machine that tracks the volume of air inhaled past the bolus, focused targeting can be maximized during a breath hold maneuver. Specifically, we visualize the motion of the pulsed SPION-laden (super-paramagnetic iron oxide nanoparticles) aerosol bolus and quantify under microscopy ensuing deposition patterns in reconstructed 3D airway models. Our aerosol inhalation platform allows for the first time to deposit inhaled particles to specific airway sites while minimizing undesired deposition across the remaining airspace, in an effort to significantly augment the targeting efficiency (i.e. deposition ratio between targeted and untargeted regions). Such inhalation strategy may pave the way for improved treatment outcomes, including reducing side effects in chemotherapy.

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“…Pourmhran et al22 simulated magnetic particle deposition in a three-dimensional reconstructed tracheobronchial airway from computed tomography scans. Deeper down the conducting airways, Martinez et al23 simulated the behavior of ellipsoidal magnetic particles in models of symmetrical terminal bronchiole bifurcations.…”

Section: Introductionmentioning

confidence: 99%

Augmenting regional and targeted delivery in the pulmonary acinus using magnetic particles

Ostrovski¹,

Hofemeier²,

Sznitman³

2016

IJN

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Background It has been hypothesized that by coupling magnetic particles to inhaled therapeutics, the ability to target specific lung regions (eg, only acinar deposition), or even more so specific points in the lung (eg, tumor targeting), can be substantially improved. Although this method has been proven feasible in seminal in vivo studies, there is still a wide gap in our basic understanding of the transport phenomena of magnetic particles in the pulmonary acinar regions of the lungs, including particle dynamics and deposition characteristics. Methods Here, we present computational fluid dynamics-discrete element method simulations of magnetically loaded microdroplet carriers in an anatomically inspired, space-filling, multi-generation acinar airway tree. Breathing motion is modeled by kinematic sinusoidal displacements of the acinar walls, during which droplets are inhaled and exhaled. Particle dynamics are governed by viscous drag, gravity, and Brownian motion as well as the external magnetic force. In particular, we examined the roles of droplet diameter and volume fraction of magnetic material within the droplets under two different breathing maneuvers. Results and discussion Our results indicate that by using magnetic-loaded droplets, 100% of the particles that enter are deposited in the acinar region. This is consistent across all particle sizes investigated (ie, 0.5–3.0 µm). This is best achieved through a deep inhalation maneuver combined with a breath-hold. Particles are found to penetrate deep into the acinus and disperse well, while the required amount of magnetic material is maintained low (<2.5%). Although particles in the size range of ~90–500 nm typically show the lowest deposition fractions, our results suggest that this feature could be leveraged to augment targeted delivery.

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Simulation of Enhanced Deposition Due to Magnetic Field Alignment of Ellipsoidal Particles in a Lung Bifurcation

Abstract: Results indicate that externally forcing local alignment of high aspect ratio particles can increase local deposition considerably.

Cited by 8 publications

References 37 publications

Magnetic particle targeting for diagnosis and therapy of lung cancers

Magnetic particle targeting for diagnosis and therapy of lung cancers

Focused targeting of inhaled magnetic aerosols in reconstructed in vitro airway models

Augmenting regional and targeted delivery in the pulmonary acinus using magnetic particles

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