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Targeting Delivery of Magnetic Aerosol Particles to Specific Regions in the Lung

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Targeting Delivery of Magnetic Aerosol Particles to Specific Regions in the Lung TARGETING DELIVERY OF MAGNETIC AEROSOL PARTICLES TO SPECIFIC REGIONS IN THE LUNG Anusmriti Ghosh B.Sc. (Mathematics), M.Sc. (Applied Mathematics) Submitted in fulfilment of the requirements for the degree of Master of Philosophy (Research) IF80 School of Chemistry, Physics and Mechanical Engineering Science and Engineering Faculty Queensland University of Technology 2018 KEYWORDS Airflow; Deposition; Deposition Concentration; Deposition Efficiency; Drug Delivery; Discrete Phase Model (DPM); Euler-Lagrange Method; Flow Rate Distribution; 2-generation Lung Model; Lung Airway; Magnetic Number; Magnetic Field; Magneto Hydro Dynamics Model (MHD); Micro Particle; Monodisperse Particle; Nano Particle; Numerical Modelling; Particle Transport; Pharmaceutical Aerosol particle; Targeted Drug Delivery; Velocity Contour. Targeting Delivery of Magnetic Aerosol Particles to Specific Regions in The Lung i ABSTRACT The inhalation of aerosol is a substantiated technique for drug delivery in the lung. Aerosolised drug inhalation plays an important role in oral and arterial routes of delivery for the treatment of respiratory diseases. A precise understanding of the aerosolised drug transport and deposition in the specific site of the lung is important as the standard dose deposit is 88% of the drug in the unwanted location of the lung. All of the published in silico, in vivo and in vitro studies have increased the knowledge of the aerosol particle transport and deposition in the human respiratory system. However, the understanding of the pharmaceutical particle deposition in the targeted region of the lung airways is still not clear. Detailed knowledge of targeting magnetic particle transport and deposition in the specific region is important, to improve the efficiency of the delivered drug and to minimise the unwanted side effects. The present study is the first-ever approach to simulate magnetic particle transport and deposition in the specific region of a 2-generation lung model by considering two different magnetic field positions. The symmetrically explicit, 2-generation lung model is generated from the geometry and mesh generation software of ANSYS 18.0. A comprehensive size- and shape-specific uniform aerosolised micro and nano-particle transport and deposition study is performed for different magnetic field positions, physical conditions and magnetic numbers for this present model. Uniform aerosolised micro and nano particle transport and deposition in the specific region of the lung airways will be reported by conducting turbulence k–ω low Reynolds number simulation. Moreover, the Magneto hydrodynamics (MHD) model is implemented and ANSYS Fluent 18.0 solver is used for targeting drug particle delivery. The aerosolised magnetic micro-particles are navigated to the targeted cell under the influence of an ii Targeting Delivery of Magnetic Aerosol Particles to Specific Regions in The Lung external magnetic force, which is applied in two different positions of the lung airways. The numerical results reveal that most particles are deposited at the targeted positions and show a new deposition technique for the lung model, which could help the targeted drug delivery in the specific region of respiratory airways. The magnetic nanoparticle transport and deposition in the specific region of the lung are investigated for a wide range of diameters (1≤nm≤500) and different flow rates. A comprehensive magnetic targeting delivery is calculated throughout the 2-generation model for two different magnetic field positions, which might be helpful for the therapeutic purpose of the lung disease patient. The numerical study performed comprehensive deposition in the targeted position. The deposition efficiency in the specific region of the lung is different for different magnetic numbers, magnetic field positions and breathing conditions, which could help the health risk assessment of respiratory diseases and eventually could help the targeted drug delivery system. The findings of the present study will help in developing better efficient drug delivery systems in affected regions of the lung airways. This process will also be cost-effective, due to systemic drug distribution in the specific region of the lung. Targeting Delivery of Magnetic Aerosol Particles to Specific Regions in The Lung iii LIST OF PUBLICATIONS Journal Paper: 1. Pharmaceutical Aerosol Transport in the Targeted Region of Human Lung Airways due to External Magnetic Field Effect. (To be submitted to Journal of Aerosol Science). 2. Targeted Drug Delivery of Magnetic Nano Particle in the Specific Region of Lung. (To be submitted to Aerosol Science and Technology). Peer Review Conference Paper: 1. Saha, S.C., Ghosh, Anusmriti, Islam, M.S., 2018. Pharmaceutical aerosol transport in the targeted position of human lung by external magnetic field. The 3rd Australian Conference on Computational Mechanics (ACCM-3), Deakin University, Waurn Ponds Campus, Melbourne, Australia, 12-14 February. (Abstract Only) iv Targeting Delivery of Magnetic Aerosol Particles to Specific Regions in The Lung TABLE OF CONTENTS KEYWORDS ............................................................................................................................ i ABSTRACT ............................................................................................................................. ii LIST OF PUBLICATIONS .................................................................................................... iv TABLE OF CONTENTS ..........................................................................................................v LIST OF FIGURES ............................................................................................................... vii LIST OF TABLES .................................................................................................................. xi LIST OF ABBREVIATIONS ................................................................................................ xii STATEMENT OF ORIGINAL AUTHORSHIP .................................................................. xiii Chapter 1 : INTRODUCTION ................................................................................. 1 1.1 BACKGROUND ............................................................................................................2 1.2 AIMS ..............................................................................................................................2 1.3 OBJECTIVES .....................................................................................................................3 1.4 SIGNIFICANCE, SCOPE AND INNOVATION...............................................................3 1.5 THESIS OUTLINE .............................................................................................................4 Chapter 2 : LITERATURE REVIEW ..................................................................... 6 2.1 BIOLOGICAL ASPECTS OF THE LUNG .......................................................................6 2.2 DEPOSITION MECHANISM ..........................................................................................11 2.3 TARGETED DRUG DELIVERY ....................................................................................12 2.3.1 PASSIVE TARGETING .....................................................................................13 2.3.2 ACTIVE TARGETING .......................................................................................14 2.4 MAGNETIC MICRO PARTICLE TRANSPORT AND DEPOSITION .........................17 2.5 MAGNETIC NANOPARTICLE TRANSPORT AND DEPOSITION............................19 2.6 SUMMARY AND IMPLICATIONS ...............................................................................22 Chapter 3 : METHODOLOGY .............................................................................. 24 3.1 ASSUMPTIONS FOR NUMERICAL SIMULATIONS .................................................26 3.2 NUMERICAL METHODOLOGY FOR CASE STUDY 1 ..............................................27 3.2.1 DRAG FORCE ....................................................................................................28 3.2.2 MAGNETIC FORCE ..........................................................................................29 3.2.2.1 EXTERNALLY IMPOSED MAGNETIC FIELD GENERATED IN NON- CONDUCTING MEDIA ............................................................................................. 30 3.3 NUMERICAL METHODOLOGY FOR CASE STUDY 2 ..............................................31 Chapter 4 : RESULTS AND DISCUSSION .......................................................... 36 4.1 CASE STUDY 1: MAGNETIC MICROPARTICLE .......................................................36 4.1.1 COMPUTATIONAL DOMAIN AND MESH GENERATION .........................36 4.1.2 GRID INDEPENDENCE TEST ..........................................................................38 Targeting Delivery of Magnetic Aerosol Particles to Specific Regions in The Lung v 4.1.3 MODEL VALIDATION ..................................................................................... 39 4.1.4 POST PROCESSING RESULTS FOR MAGNETIC MICRO-PARTICLE ...... 43 4.2 CASE STUDY 2: MAGNETIC NANOPARTICLE ........................................................ 56 4.2.1 COMPUTATIONAL DOMAIN AND MESH GENERATION: ....................... 56 4.2.2 GRID INDEPENDENCE TEST: ........................................................................ 57 4.2.3 MODEL VALIDATION:...................................................................................
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