Magnetic drug targeting through a realistic model of human tracheobronchial airways using computational fluid and particle dynamics

Magnetic drug targeting (MDT) is a local drug delivery system which aims to concentrate a pharmacological agent at its site of action in order to minimize undesired side effects due to systemic distribution in the organism. Using magnetic drug particles under the influence of an external magnetic field, the drug particles are navigated toward the target region. Herein, computational fluid dynamics was used to simulate the air flow and magnetic particle deposition in a realistic human airway geometry obtained by CT scan images. Using discrete phase modeling and one-way coupling of particle–fluid phases, a Lagrangian approach for particle tracking in the presence of an external non-uniform magnetic field was applied. Polystyrene (PMS40) particles were utilized as the magnetic drug carrier. A parametric study was conducted, and the influence of particle diameter, magnetic source position, magnetic field strength and inhalation condition on the particle transport pattern and deposition efficiency (DE) was reported. Overall, the results show considerable promise of MDT in deposition enhancement at the target region (i.e., left lung). However, the positive effect of increasing particle size on DE enhancement was evident at smaller magnetic field strengths (Mn $$\le $$≤ 1.5 T), whereas, at higher applied magnetic field strengths, increasing particle size has a inverse effect on DE. This implies that for efficient MTD in the human respiratory system, an optimal combination of magnetic drug career characteristics and magnetic field strength has to be achieved.

[1]  B. Belkassem,et al.  Large eddy and detached eddy simulations of fluid flow and particle deposition in a human mouth–throat , 2008 .

[2]  Samir Vinchurkar,et al.  Validating CFD predictions of respiratory aerosol deposition: effects of upstream transition and turbulence. , 2007, Journal of biomechanics.

[3]  Mir Behrad Khamesee,et al.  Magnetic targeting of aerosol particles for cancer therapy , 2005 .

[4]  Bernhard Gleich,et al.  Targeted delivery of magnetic aerosol droplets to the lung , 2007, Nature Nanotechnology.

[5]  Ewald R. Weibel,et al.  Geometry and Dimensions of Airways of Conductive and Transitory Zones , 1963 .

[6]  Benjamin Y. H. Liu,et al.  Experimental Study of Particle Deposition in Bends of Circular Cross Section , 1987 .

[7]  C. Kleinstreuer,et al.  Simulation of airflow fields and microparticle deposition in realistic human lung airway models. Part I: Airflow patterns , 2007 .

[8]  S. A. Morsi,et al.  An investigation of particle trajectories in two-phase flow systems , 1972, Journal of Fluid Mechanics.

[9]  G. Ahmadi,et al.  Particle deposition in turbulent duct flows—comparisons of different model predictions , 2007 .

[10]  Michael Breuer,et al.  Prediction of aerosol deposition in 90∘ bends using LES and an efficient Lagrangian tracking method , 2006 .

[11]  J. Ally Magnetically targeted deposition and retention of particles in the airways for drug delivery , 2010 .

[12]  Alfredo Soldati,et al.  Experimental investigation on interactions among fluid and rod-like particles in a turbulent pipe jet by means of particle image velocimetry , 2014, Experiments in Fluids.

[13]  D. Wen,et al.  Flow and migration of nanoparticle in a single channel , 2009 .

[14]  W. K. Morgan,et al.  Differences in particle deposition between the two lungs. , 1995, Respiratory medicine.

[15]  C Kleinstreuer,et al.  Targeted drug aerosol deposition analysis for a four-generation lung airway model with hemispherical tumors. , 2003, Journal of biomechanical engineering.

[16]  C. Graham,et al.  Introduction to Magnetic Materials , 1972 .

[17]  Clement Kleinstreuer,et al.  Airflow and Particle Transport in the Human Respiratory System , 2010 .

[18]  Christopher J. Elkins,et al.  Three-dimensional inspiratory flow in the upper and central human airways , 2015 .

[19]  C. Rudolph,et al.  Respiration triggered magnetic drug targeting in the lungs , 2009, 2009 Annual International Conference of the IEEE Engineering in Medicine and Biology Society.

[20]  Mofid Gorji-Bandpy,et al.  CFD simulation of airflow behavior and particle transport and deposition in different breathing conditions through the realistic model of human airways , 2015 .

[21]  Mofid Gorji-Bandpy,et al.  Simulation of magnetic drug targeting through tracheobronchial airways in the presence of an external non-uniform magnetic field using Lagrangian magnetic particle tracking , 2015 .

[22]  C. G. Phillips,et al.  The influence of the branching pattern of the conducting airways on flow and aerosol deposition parameters in the human, dog, rat and hamster , 1997 .

[23]  Ananth V. Annapragada,et al.  Computational Fluid Dynamics Simulation of Airflow and Aerosol Deposition in Human Lungs , 2004, Annals of Biomedical Engineering.

[24]  M. Sommerfeld,et al.  Multiphase Flows with Droplets and Particles , 2011 .

[25]  Clement Kleinstreuer,et al.  Low-Reynolds-Number Turbulent Flows in Locally Constricted Conduits: A Comparison Study , 2003 .

[26]  R. Tiner,et al.  Aerosol drug delivery: developments in device design and clinical use , 2011, The Lancet.

[27]  Carsten Rudolph,et al.  First Theoretic Analysis of Magnetic Drug Targeting in the Lung , 2010, IEEE Transactions on Biomedical Engineering.

[28]  M. Mohammadpourfard,et al.  Numerical study of the ferrofluid flow and heat transfer through a rectangular duct in the presence of a non-uniform transverse magnetic field , 2013 .

[29]  Ravi P Subramaniam,et al.  Analysis of Lobar Differences in Particle Deposition in the Human Lung , 2003, Inhalation toxicology.

[30]  C. Plank Nanomagnetosols: magnetism opens up new perspectives for targeted aerosol delivery to the lung. , 2008, Trends in biotechnology.

[31]  Miroslav Jicha,et al.  Numerical investigation of inspiratory airflow in a realistic model of the human tracheobronchial airways and a comparison with experimental results , 2016, Biomechanics and modeling in mechanobiology.

[32]  J. Mulshine,et al.  Inhaled isotretinoin (13-cis retinoic acid) is an effective lung cancer chemopreventive agent in A/J mice at low doses: a pilot study. , 2000, Clinical cancer research : an official journal of the American Association for Cancer Research.

[33]  Goodarz Ahmadi,et al.  Brownian diffusion of submicrometer particles in the viscous sublayer , 1991 .