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
Targeting Delivery of Magnetic Aerosol Particles to Specific Regions in The Lung i
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.
ii Targeting Delivery of Magnetic Aerosol Particles to Specific Regions in The Lung
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
Targeting Delivery of Magnetic Aerosol Particles to Specific Regions in The Lung iii
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.
iv Targeting Delivery of Magnetic Aerosol Particles to Specific Regions in The Lung
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)
Targeting Delivery of Magnetic Aerosol Particles to Specific Regions in The Lung v
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
vi Targeting Delivery of Magnetic Aerosol Particles to Specific Regions in The Lung
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:.................................................................................... 57 4.2.4 POST PROCESSING RESULTS FOR MAGNETIC NANOPARTICLE ......... 59
Chapter 5 : CONCLUSIONS .................................................................................. 74
5.1 CONCLUSIONS .............................................................................................................. 74
5.2 LIMITATIONS AND FUTURE STUDY ........................................................................ 76
BIBLIOGRAPHY ..................................................................................................... 77
APPENDICES .......................................................................................................... 83
A: CASE STUDY 1 (MAGNETIC MICRO PARTICLE) ..................................................... 83 A1: MESH GENERATION ......................................................................................... 83 A2: FLOW RATES EFFECT ...................................................................................... 84 A3: PARTICLE DIAMETER EFFECT ....................................................................... 85 A4: MAGNETIC FIELD (POSITION) EFFECT ........................................................ 86
B: CASE STUDY 2 (MAGNETIC NANO PARTICLE) ...................................................... 87 B1: EFFECT OF FLOW RATES ON PARTICLE TD FOR MAGNETIC
FIELD POSITION1, MN=2.5 AND DIFFERENT PARTICLE
DIAMETER ....................................................................................................... 87 B2: EFFECT OF FLOW RATES ON PARTICLE TD FOR MAGNETIC
FIELD POSITION 2, MN=2.5 AND DIFFERENT PARTICLE
DIAMETE ......................................................................................................... 88 B3: PARTICLE DIAMETER AND MAGNETIC POSITION EFFECT FOR
MN=0.18 AND 15 LPM FLOW RATES .......................................................... 89 B4: DEPOSITION EFFICIENCY HISTOGRAM FOR MAGNETIC FIELD
POSITION 1 ...................................................................................................... 90 B5: DEPOSITION EFFICIENCY HISTOGRAM FOR MAGNETIC FIELD
POSITION 2 ...................................................................................................... 90 B6: REGIONAL DEPOSITION EFFICIENCY FOR 15 LPM AND MN 0.181 ........ 91 B7: REGIONAL DEPOSITION EFFICIENCY FOR 15 LPM AND MN 1.5 ............ 92 B8: STATIC PRESSURE FOR POSITION 2 ............................................................. 92
Targeting Delivery of Magnetic Aerosol Particles to Specific Regions in The Lung vii
LIST OF FIGURES
Figure 1.1 Flowchart of the present thesis. .................................................................. 5
Figure 2.1 Human respiratory system ("Human body. Reaspiratory system
diagram. Retrieved April 6, 2017, from
http://www.buzzle.com/images/diagrams/human-body/respiratory-
system-diagram.jpg," 2017). .......................................................................... 7
Figure 2.2 (a) Structural design of lung components (b) The segmented view of
the computational domain (Rahimi-Gorji et al., 2016). ................................. 8
Figure 2.3 Picture of human lung with alveoli. (Matthew Hoffman, 2014). ............... 9
Figure 2.4 Particle size that enters into the respiratory system ("Respiratory
system. Retrieved April 6, 2017, from
http://www.livescience.com/22616-respiratorysystem.html,") (This
figure has been modified.) ........................................................................... 10
Figure 2.5 Action of nanomagnetosols Mechanism (Plank, 2008). ......................... 14
Figure 2.6 Schematic representation of magnetic nanoparticle microcomposites
(MnMs) by pulmonary delivery (Stocke et al., 2015). ................................ 16
Figure 2.7 Advantages and challenges of pulmonary drug delivery (Kuzmov &
Minko, 2015)................................................................................................ 17
Figure 3.1: Framework of the present thesis. ............................................................. 25
Figure 4.1 (a) Anterior view of the 2-generation mesh with 179,660
unstructured cells, (b) first bifurcation, (c) inlet mesh, (d) inflation
layer mesh near to the wall, (e) terminal bronchioles mesh, (f) outlet
mesh of 2 generation lung model. ................................................................ 37
Figure 4.2 Maximum velocity grid convergence ....................................................... 39
Figure 4.3 Present simulated particle deposition efficiency comparison with the
experimental data of (Cheng et al., 2010) and (Kleinstreuer et al.,
2008). ........................................................................................................... 40
Figure 4.4 Particle deposition fraction comparison between the present
simulation data with the experimental different data sets of
(Kleinstreuer et al., 2008), Chen et al.,(1999), (Lippmann & Albert,
1969), (Chan & Lippmann, 1980), Foord et al., (1978), (Stahlhofen et
al., 1980) , Stahlhofen et al., (1983), (Emmett et al., 1982) and
(Bowes & Swift, 1989). ............................................................................... 40
Figure 4.5 Geometry specification. (Magnet position 2 has been set on the left
lung) ............................................................................................................. 41
Figure 4.6 Particle deposition efficiency using magnetic position comparison
between the present simulation and experimental data sets of (Cohen,
2009), (Haverkort, 2008), and (Oveis Pourmehran et al., 2016) ................. 42
Figure 4.7 Velocity profiles in the symmetric bifurcation airway model for
steady inhalation with Q= 60 lpm. (a) Contour of velocity magnitude
viii Targeting Delivery of Magnetic Aerosol Particles to Specific Regions in The Lung
for (a) 2- generation lung model; (b ) Left outlet 1and (c) Left outlet 2;
(d) Right outlet 1and (e) Right outlet 2. ....................................................... 43
Figure 4.8: Contour of Magnetic source for Mn=2.5T (a) position 1; (b)
position 2. Particle traces coloured by particle residence time for (c)
Position 1; (d) Position 2. ............................................................................. 44
Figure 4.9 Turbulent kinetic energy of magnitude contour for (a) position 2; (b)
position 1; Particle traces coloured by (c) velocity magnitude for
position 1; (d) velocity magnitude for position 2. ........................................ 46
Figure 4.10 Effect of flow rates on particle transport outline and DE (%) for
Position 2, 𝑑𝑝 = 4 𝜇𝑚, 𝑀𝑛 = 2.5 𝑇, (a) 15 lpm; (b) 30 lpm; (c) 60
lpm; (d) Total deposition efficiency in terms of flow rates. ........................ 47
Figure 4.11 Particle diameter effect on particle transport outline and DE (%)
for position 2, 𝑀𝑛 = 2.5 𝑇, Q=60 lpm (a) 𝑑𝑝 = 2 𝜇𝑚; (b) 𝑑𝑝 =4 𝜇𝑚; (c) 𝑑𝑝 = 6 𝜇𝑚; (d) overall deposition efficiency. ............................ 49
Figure 4.12: Magnetic number effect (Flux value) on particle transport outline
and DE (%) for Position 2, 𝑑𝑝 = 4 𝜇𝑚, Q=60lpm,(a) 𝑀𝑛 =0.181T;(b)𝑀𝑛 = 2.5 T; (c)𝑀𝑛 = 3 T; (d) deposition efficiency for
magnetic number. ......................................................................................... 51
Figure 4.13: Effect of source position of magnet on particle transport outline
and DE (%) for 𝑑𝑝 = 4 𝜇𝑚, Q=30 lpm, 𝑀𝑛 = 2.5 𝑇, (a) Position
1; (b) Position 2;(c) deposition efficiency for magnetic source
position. ........................................................................................................ 53
Figure 4.14: Local deposition efficiency for (a) flow rates; (b) Particle
diameter; (c) Magnetic number effect; (d) Magnetic source position.
Generation 1 (g1), Left Generation 2 (lg2); Right Generation 2 (rg2). ....... 54
Figure 4.15: (a) Anterior view of the 2-generation mesh with 0.54 million
unstructured cells, (b) interior view and inflation layer mesh near to
the wall, (c) inlet mesh, (d) outlet mesh of 2-generation lung model. ......... 56
Figure 4.16: Maximum pressure grid convergence .................................................... 57
Figure 4.17. Nano-particle DE comparison with the experimental data of Kim
(2002) and the CFD results of Zhang and Kleinstreuer (2004) and
(Islam et al., 2017), in a double bifurcation model (G3-G5), (a) first
bifurcation, and (b) second bifurcation. ....................................................... 58
Figure 4.18 Deposition fraction (DF) of Nano-particle comparison with the
CFD results of Zhang and Kleinstreuer (2004) across different
bifurcation for 30 lpm flow rates in the bifurcation airway model. ............. 58
Figure 4.19: Geometry specification of 2-generation model (Magnet position 2
has been set on the right lung). .................................................................... 59
Figure 4.20: Effect of Flow Rates on particle transport outline for position 1
and position 2, Mn=2.5 T, dp=1-nm, (a) 7.5 lpm for position 1; (b) 7.5
lpm for position 2; (c) 9 lpm for position 1; (d) 9 lpm for position 2;
(e) 15 lpm for position 1; (f) 15 lpm for position 2; (g) Overall
deposition efficiency. ................................................................................... 60
Targeting Delivery of Magnetic Aerosol Particles to Specific Regions in The Lung ix
Figure 4.21: Effect of magnetic number on particle transport outline for
Position 1 and position 2, 7.5 lpm, dp=1-nm, (a) Mn=0.181 T for
position 1; (b) Mn=0.181T for position 2 ; (c) Mn=1.5 T for position
1; (d) Mn=1.5 T for position 2; (e) Mn=2.5 T for position 1; (f)
Mn=2.5 T for position 2; (g) Overall deposition efficiency for
magnetic position 1 and magnetic position 2. .............................................. 62
Figure 4.22: Particle Traces Coloured by Turbulent Kinetic Energy (k)
(𝑚2/𝑆2) for 60 lpm, Mn=2.5 T and magnet position 2, (a) 1- nm; (b)
10- nm; (c) 50- nm; (d) 100- nm; (e) 500- nm. ............................................ 64
Figure 4.23: Particle Traces Coloured by particle residence time at magnetic
position 2 for 60 lpm and Mn=2.5 T (a) 1- nm; (b) 10- nm; (c) 50- nm;
(d) 100- nm; (e) 500- nm. ............................................................................ 66
Figure 4.24: Deposition Efficiency comparisons for nano particles of various
diameter and flow rates at position 1 and position 2 for magnetic
number 2.5 T. ............................................................................................... 68
Figure 4.25: Deposition Efficiency comparisons for nano particles of various
diameters and magnetic number at position 1 and position 2 for 15
lpm flow rates. ............................................................................................. 70
Figure 4.26: Regional particle deposition efficiency in each zone at different
particle sizes, magnet position, magnetic number 2.5 T and inhalation
rates. Generation 1 (g1), Left Generation 2 (lg2), Right Generation 2
(rg2).............................................................................................................. 72
Figure A.1: (a) interior view of the 2-generation mesh. ............................................ 83
Figure A.2: Effect of flow rates on particle transport outline and DE (%) for
Position 2, 𝑑𝑝 = 4 𝜇𝑚, 𝑀𝑛 = 0.25 𝑇 , (a) 15 lpm; (b) 30 lpm; (c) 60
lpm; (d) Total deposition efficiency in terms of flow rates. ........................ 84
Figure A.3: Effect of particle diameter on particle transport outline and DE (%)
for Position 2, 𝑀𝑛 = 0.25 𝑇, Q=60 lpm (a) 𝑑𝑝 = 2 𝜇𝑚; (b) 𝑑𝑝 =4 𝜇𝑚; (c) 𝑑𝑝 = 6 𝜇𝑚; (d) deposition efficiency. ........................................ 85
Figure A.4: Effect of magnetic field on particle TD outline for (a) position 1;
(b) particle traces by particle id for magnet position 2. ............................... 86
Figure A.5: Magnitude of 𝐵 (magnetic flux density) vector for position 2. ............. 86
Figure A.6: Effect of flow rates on particle transport outline for particle
diameter 1-nm, 10- nm, 50-nm,100-nm,500-nm, position 1, Mn=2.5T,
(a) 1-nm for 7.5 lpm; (b) 10-nm for 7.5 lpm; (c) 50-nm for 7.5 lpm;
(d) 100-nm for 7.5 lpm; (e) 500-nm for 7.5 lpm; (f) 1-nm for 9 lpm;
(g) 10-nm for 9 lpm; (h) 50-nm for 9 lpm; (i) 100-nm for 9 lpm; (j)
500-nm for 9 lpm; (k) 1-nm for 15 lpm; (l) 10-nm for 15 lpm; (m) 50-
nm for 15 lpm; (n) 100-nm for 15 lpm; (o) 500-nm for 15 lpm; (p) 1-
nm for 60 lpm; (q) 10-nm for 60 lpm; (r) 50-nm for 60 lpm; (s) 100-
nm for 60 lpm; (t) 500-nm for 60 lpm. ........................................................ 87
Figure A.7: Effect of flow rates on particle transport outline for particle
diameter 1-nm, 10- nm, 50-nm,100-nm,500-nm, position 2, Mn=2.5T,
(a) 1-nm for 7.5 lpm; (b) 10-nm for 7.5 lpm; (c) 50-nm for 7.5 lpm;
(d) 100-nm for 7.5 lpm; (e) 500-nm for 7.5 lpm; (f) 1-nm for 9 lpm;
x Targeting Delivery of Magnetic Aerosol Particles to Specific Regions in The Lung
(g) 10-nm for 9 lpm; (h) 50-nm for 9 lpm; (i) 100-nm for 9 lpm; (j)
500-nm for 9 lpm; (k) 1-nm for 15 lpm; (l) 10-nm for 15 lpm; (m) 50-
nm for 15 lpm; (n) 100-nm for 15 lpm; (o) 500-nm for 15 lpm; (p) 1-
nm for 60 lpm; (q) 10-nm for 60 lpm; (r) 50-nm for 60 lpm; (s) 100-
nm for 60 lpm; (t) 500-nm for 60 lpm. ........................................................ 88
Figure A.8: Effect of particle diameter and magnet position on particle
transport outline Mn= 0.18T, flow rates 15 lpm, (a) 1-nm for position
1; (b) 1-nm for position 2; (c) 10-nm for position 1; (d) 10-nm for
position 2; (e) 50-nm for position 1; (f) 50-nm for position 2. .................... 89
Figure A.9: Deposition Efficiency comparisons for NPs of various diameter
and flow rates at position 1 for magnetic number 2.5T. .............................. 90
Figure A.10: Deposition Efficiency comparisons for NPs of various diameter
and flow rates at position 2 for magnetic number 2.5T. .............................. 90
Figure A.11: Regional particle deposition efficiency in each zone at different
particle sizes, magnet position, magnetic number 0.181T and 15 lpm
flow rates. ..................................................................................................... 91
Figure A.12: Regional particle deposition efficiency in each zone at different
particle sizes, magnet position, magnetic number 1.5 T and 15 lpm
flow rates. ..................................................................................................... 92
Figure A.13: Static pressure for position 2, Mn=2.5 T, 1-nm, 9 lpm......................... 92
Targeting Delivery of Magnetic Aerosol Particles to Specific Regions in The Lung xi
LIST OF TABLES
Table 4.1. Respiratory particle TD comparisons for 1-, 50-, 100- and 500-nm
diameter particles as a function of different breathing airflow rates and
magnetic number 2.5T.Posi 1(position 1), Posi 2 (position 2). ................... 68
Table 4.2. Respiratory particle TD comparisons at two different targeted
positions for 0.181 T, 1.5 T, and 2.5 T magnetic number as a function
of 15lpm breathing airflow rates and 1-, 50-, 100- and 500-nm
diameter particle........................................................................................... 70
xii Targeting Delivery of Magnetic Aerosol Particles to Specific Regions in The Lung
LIST OF ABBREVIATIONS
CFD Computational Fluid Dynamic
CF Cystic Fibrosis
COPD Chronic Obstructive Pulmonary Disease
CT Computerized Tomography
DDS Drug Delivery Systems
DE Deposition Efficiency
DF Deposition Fraction
DPM Discrete Phase Model
3DCRT 3-Dimension Conformal Radiation Therapy
E-L Euler-Lagrange
IMRT Intensity Modulated Radiation Therapy
LPM Litre Per Minute
MHD Magneto hydro-dynamics
MRI Magnetic Resonance Imaging
Mn Magnetic Number (Tesla)
MNPs Magnetic Nanoparticles
MnMs Magnetic Nanoparticle Microcomposites
MMAD Mass Median Aerosol Diameter
NPs Nano Particles
PMDIs Pressurized Meter Dose Inhalers
TD Transport and Deposition
VMAT Volumetric Modulated Arc Therapy
Targeting Delivery of Magnetic Aerosol Particles to Specific Regions in The Lung xiii
STATEMENT OF ORIGINAL AUTHORSHIP
The work contained in this thesis has not been previously submitted to meet
requirements for an award at this or any other higher education institution. To the best
of my knowledge and belief, the thesis contains no material previously published or
written by another person except where due reference is made.
Signature:
Date: 27/03/2018
QUT Verified Signature
xiv Targeting Delivery of Magnetic Aerosol Particles to Specific Regions in The Lung
ACKNOWLEDGEMENTS
I would like to express my gratitude, appreciation, and deepest sense of indebtedness
to my supervisor, Dr Suvash C. Saha, for his willingness to accept me as a MPhil
student. He has helped me to carry out my thesis work on this challenging topic and
also has aided me through his patience, motivation, enthusiasm, constructive criticism,
and endless encouragement during the completion of the thesis.
I would like to convey my gratitude to my other supervisor, Professor Richard Brown,
for his support throughout my candidature. I would like to acknowledge them both, for
their valuable insight, continuous encouragement, motivation and belief in my ability.
I want to thank Mohammad Saidul Islam, for his help to me in conducting this research.
The high performance computing facility in QUT is also acknowledged.
Professional editor, Diane Kolomeitz, provided copyediting and proofreading services,
according to the guidelines laid out in the university-endorsed national guidelines for
editing research theses.
Thanks also to all my friends in QUT and here in Brisbane for their support.
Finally, last but not least, I would like to acknowledge family members, not only for
this MPhil journey, but also for their contribution to my whole life.
Targeting Delivery of Magnetic Aerosol Particles to Specific Regions in The Lung 1
Chapter 1 : INTRODUCTION
The lung is one of the unique organs of the human body involved in oxidative
stress, because it flexibly brings down higher oxygen pressures. Lung cells involve
enriched oxidant pressure because of their direct exposure to ambient air by
environmental irritants and pollutants (Kinnula & Crapo, 2003). The inhaled air is
consumed to transfer aerosolized drug particles into the lungs, in the therapeutic
supervision of lung diseases. A predicted number of lung disorder patients increasing
over the next two decades means different types of therapeutic techniques are being
established to maximise treatments. These are techniques such as Intensity Modulated
Radiation Therapy (IMRT), 3-Dimension Conformal Radiation Therapy (3DCRT),
Volumetric Modulated Arc Therapy (VMAT) and chemotherapy. All of these aim is
to deliver drugs to the affected area. There are very limited studies that have been
conducted on magnetic aerosol particles or drug aerosols for targeting magnetic drug
delivery in the specific region of the lungs. In the present study, an advanced magnetic
aerosol particle transport and deposition (TD) model has been developed for the first
time, for better prediction of drug delivery in the affected area of lung airways for a 2-
generation, symmetrical lung model.
This chapter outlines the background (section 1.1) and aims (section 1.2) of the
research, and its objectives (section 1.3). Section 1.4 describes the significance and
scope of this research and provides definitions of terms used. Finally, section 1.5
includes an outline of the remaining chapters of the thesis.
2 Chapter 1: Introduction
1.1 BACKGROUND
Magnetic aerosol has gained much attention among researchers for targeting
local drug delivery to minimise undesired side effects in the organism. The most
common lung diseases today are asthma, cystic fibrosis, chronic obstructive
pulmonary disease (COPD), respiratory infection and lung cancer. Magnetic targeting
of drugs is especially attractive for chemotherapy. Chemotherapy is an ideal
application of drug delivery for localised targeted sites via inhaled aerosol. Targeting
delivery of magnetic aerosol by an external magnetic field is such a drug delivery
system, by which the drug is usually concentrated in a specific, targeted site. This
process also minimizes the total drug dosage required, and decreases systemic toxicity
as well as treatment cost. Even though enormous progress has been made in improving
aerosol supply to the lung, magnetisable, targeted aerosol supply to the specific
regions in the lung other than the lung periphery or airways has not been sufficiently
achieved up to date (Dames et al., 2007). A precise understanding of magnetic particle
transport and deposition in a specific region of the lung is important for respiratory
health risk assessment. Therefore, a magnetic aerosol particle TD study is necessary
for better prediction of the pharmaceutical aerosol delivery to the targeted position of
the lung airways. Hence, detailed analyses of magnetic aerosol particles or drug
aerosol transport and deposition phenomena in the human respiratory tract are needed,
for a better understanding of the fluid-particle dynamics and aerosol drug impact
studies.
1.2 AIMS
The aim of this study is to develop an advanced numerical model to analyse the
magnetic field intensity, numerical methods for determining the overall algorithm of
Targeting Delivery of Magnetic Aerosol Particles to Specific Regions in The Lung 3
magnetic therapeutic aerosol targeting in a specific region of the lung, effects of
particle diameter and inhalation flow rate for targeting magnetic drug aerosol
deposition in a specific region of the lung, to guide the improvement and testing of
novel therapies for lung disease.
1.3 OBJECTIVES
To achieve the aims of this study, the following objectives need to be addressed:
• Generate a 2-generation human lung geometry for determining the
accurate flow of magnetic aerosol particles;
• Develop an advanced numerical method and algorithm to guide
magnetic therapeutic aerosol towards a specific targeted region of the
lung;
• Investigate the effect of particle shape and size, magnetic source
position, strength of magnetic field and inhalation flow rate on the
transport and deposition in the targeted lung region for micro and nano
particles;
• Study the magnetic intensity in the specific region of the lung and
investigate the magnetic micro and nano particle deposition pattern in
the targeted position of a 2-generation symmetric lung model.
1.4 SIGNIFICANCE, SCOPE AND INNOVATION
A precise understanding of the size and shape-specific magnetic aerosol particle
transport and deposition is the principal step in the assessment of a respiratory health
hazard and more efficient drug aerosol delivery in the pulmonary airways. This thesis
presents a comprehensive and advanced computational analysis of magnetic targeting
4 Chapter 1: Introduction
drug delivery or drug aerosol transport and uptake in the specific airways of a 2-
generation symmetrical model for the first time. The deposition efficiency (DE) of
different diameter particles, as a function of various deposition parameters, are
investigated for this 2- generation lung model. The specific findings of the present
study advance the field and improve the understanding of therapeutic aerosol transport
to the specific targeted region of the airways. The magnetic aerosol particle TD study
will improve the efficiency of the delivered drug to the targeted position of the lung
and could potentially guide the development of future targeted drug delivery systems.
The magnetic nano particles (MNPs)’ TD analysis improves the knowledge of the
nanoparticle (NPs) deposition pattern at the specific region of lung and this could
possibly help to design new drug delivery devices. The advanced computational study
could be used for clinical assessment of respiratory diseases. The new framework can
be used to minimise the efficiency of the dose deposition at the unwanted region and
unwanted site effects of the lung airways. This study enhances the knowledge of
magnetic particle flow in different biomechanical engineering applications.
The present study develops a 2-generation symmetric model for more accurate
prediction of the particulate deposition in a specific region of the lung, by an external
magnetic field. This study develops a new framework to predict and analyse the
realistic deposition pattern, which would potentially help to understand the deposition
mechanism. This first-ever study investigates monodisperse microparticle and nano-
particle TD in the specific region of the lung by external magnetic field.
1.5 THESIS OUTLINE
This thesis structure is as follows: Introduction (Chapter 1), Literature review
(Chapter 2), Methodology (Chapter 3) based on Case study 1(Magnetic Micro particle)
Targeting Delivery of Magnetic Aerosol Particles to Specific Regions in The Lung 5
and case study 2 (Magnetic Nano particle) and its Results and Discussion in Chapter
4, regarding this case study 1 and case study 2. Finally, Chapter 5 describes the
conclusions of the thesis.
The overall outline of this thesis is shown in figure 1.1.
Figure 1.1 Flowchart of the present thesis.
6 Chapter 3: Methodology
Chapter 2 : LITERATURE REVIEW
In this chapter, the overall biological aspects of the lung and the development of
magnetic drug delivery are summarised. The different aspects of targeted drug delivery
are also discussed. This chapter begins with the biological aspects of the lung and the
content includes
Biological aspects of the lung;
Deposition mechanism;
Targeted drug delivery;
Magnetic Microparticle transport and deposition;
Magnetic Nanoparticle transport and deposition.
2.1 BIOLOGICAL ASPECTS OF THE LUNG
Due to the biomechanical and real life application of human lung research,
most of the researchers in the field have an ample keenness towards human lung
modelling and simulation. The human lung is a respiratory organ consisting of two
spongy parts (Gray & Goss, 1878). Respiration is essential for both plant and animal
cells, including human, to survive. Respiration happens through a group of organs
forming the respiratory system. The lung is the main organ of breathing. Gas exchange
is the fundamental role of the respiratory system, which helps our body to keep a
balance in supplying oxygen to red blood cells and expelling carbon dioxide into the
environment (Ratnovsky et al., 2008).
Targeting Delivery of Magnetic Aerosol Particles to Specific Regions in The Lung 7
The organs of the respiratory system are divided into two parts (Fig.2.1); one is
the upper respiratory tract and the other one is the lower respiratory tract. The upper
respiratory tract consists of mainly the nose, nasal cavity and pharynx, where the
lower consists of larynx, trachea, bronchial tree and lung (Ionescu, 2013).
All the above components play an inevitable contribution to supply oxygen into blood
cells and expel the carbon-dioxide from the lung. The total surface area of the lung is
about half of a tennis court and considered to be between 80 m2 and 140 m2 (Scheuch
et al., 2006).
The human cell needs a flow stream of oxygen for its existence and to release the
carbon dioxide, which is a waste product of the human body mechanism. The
respiratory system is responsible for oxygen supply to the body cells and the removal
of carbon dioxide. The nose, mouth, pharynx, larynx, trachea, bronchi, and
bronchioles are the components of the airway system (Fig.2.2 a). The segmented
Figure 2.1 Human respiratory system ("Human body. Reaspiratory system diagram.
Retrieved April 6, 2017, from http://www.buzzle.com/images/diagrams/human-
body/respiratory-system-diagram.jpg," 2017).
8 Chapter 3: Methodology
meshing view of the computational domain is shown in fig 2.2(b). The human lung
acts as a working unit of the respiratory system.
The human airway starts with the trachea, then bronchi and bronchioles, with a total
of about 23 to 32 generations that finally end at the alveoli (Mortensen et al., 2014).
The lung consists of spongy-like textures. These textures are full of air organs that are
located on both side of the chest (thorax). The trachea transports the inhaled air into
the lung through the bronchi. Then the bronchi partition into smaller and smaller
branches, called bronchioles and finally, they become microscopic (Fig.2.3). The
alveoli, microscopic air sacs at the end of the bronchioles, absorb oxygen (Gray &
Figure 2.2 (a) Structural design of lung components (b) The segmented view of the
computational domain (Rahimi-Gorji et al., 2016).
Targeting Delivery of Magnetic Aerosol Particles to Specific Regions in The Lung 9
Goss, 1878; Tomlinson et al., 1994) from the air (Denison et al., 1982) and transport
into the blood.
These bronchioles ultimately end in bunches of microscopic air bags called alveoli
(Fig.2.3). Alveoli mainly absorb oxygen from the air. Carbon dioxide is a waste
product of metabolism, which travels from the blood to the alveoli and then it can be
exhaled. Interstitium is a thin layer of cells between the alveoli, which covers blood
vessels. The alveoli surface is covered by water-based alveolar fluid. During inhaling
and exhaling, the alveoli expand and compress.
In the time of an inhalation process, an adult human inhales somewhere
between 100 bi1lion and 10 trillion particles per day with oxygen (Tsuda et al., 2013).
Particles sized less than 100µm are only able to enter into the body by inhalation
(Fig.2.4). Particles between 10 µm to100µm in size are cleared out by nasal hairs, nasal
Figure 2.3 Picture of human lung with alveoli. (Matthew Hoffman, 2014).
10 Chapter 3: Methodology
mucosa or mucus that always moves up by cilia in the bronchi and bronchioles. Less
than 10 µm can pass through the above-mentioned barriers and travel into the
pulmonary region of the lung (Fig.2.4). Among these particles, only ultrafine particles
(<100nm) are consider most harmful (Anseth et al., 2005; N. Li et al., 2003; Sioutas
et al., 2005) and can create many health hazards, particularly in the lung. The health
hazards include Asbestosis (Shipyard, Mine and Mill workers), Benign
pneumoconiosis (Iron miners, Tin workers and Welders), Beryllium disease
(Aerospace and Metallurgical workers), Occupational asthma (Grains and Tea farm
workers), Silicosis (Foundry, Tunnel workers, Potters and Farmers)
(" Lung diseases. Environmental lung diseases. Retrieved April 6, 2017, from
http://www.merckmanuals.com/home/lungand-airway-disorders/environmental-lung-
diseases/overview-of-environmental-lungdiseases,").
Figure 2.4 Particle size that enters into the respiratory system ("Respiratory
system. Retrieved April 6, 2017, from http://www.livescience.com/22616-
respiratorysystem.html,") (This figure has been modified.)
Particle size µm <100
Particle size < µm 10
Targeting Delivery of Magnetic Aerosol Particles to Specific Regions in The Lung 11
Some of these particles are soluble and may be dissolved into the bloodstream.
Therefore, these types of particles have the ability to penetrate all the defense
mechanisms of the lung, whereas, the other type of particles that are insoluble are
mostly cleared by mucus, cilia or macrophages. Only a few of the insoluble particles
can reach deep into the lung by penetrating the defense mechanisms of the respiratory
system, which has a negative effect on human health.
2.2 DEPOSITION MECHANISM
The human lung is instinctively an integral part of the chest. The human lung
cell is very important for particle transport and deposition. The particulate deposition
in the human lung has become one of the interesting topics for researchers, for its
practical application in medical science. Investigating the deposition pattern of
inhaled particles in the human lung is very challenging due to the complex geometrical
structure of the human lung (H. Kumar et al., 2009; Soni & Aliabadi, 2013; Weibel,
1963). Computational fluid dynamics (CFD) models are able to determine the high
deposition efficiency.
In recent years, several geometric models of the human lung have been
developed. In the case of modelling and simulation of particle deposition in human
lung cells, Weibel’s (Weibel, 1963) lung model is still being used, due to its geometric
simplicity. Because of the limitations of the idealised lung models, most of the
experimentalists and CFD analysts now focus on realistic airway models to determine
the particle deposition in the human lung (H. Kumar et al., 2009; Ma & Lutchen, 2006,
2009). Anatomically based human airway models, like the Computerized Tomography
(CT) scan or Magnetic Resonance Imaging (MRI) geometrical model, attract current
12 Chapter 3: Methodology
researchers. In order to investigate accurate particle deposition patterns in the human
lung, realistic deposition models are very effective (B Asgharian et al., 2001).
Inhaled particle deposition in the human lung is mainly caused by Brownian
diffusion, gravitational sedimentation and inertial impaction (Choi & Kim, 2007).
Inhaled particle deposition in the human respiratory tract is mainly governed by its
shape (W Hofmann et al., 2009; Kasper, 1982) and size (Werner Hofmann, 2011).
The particulates >5 µm are deposited in the oropharynx and the particles 1-5 µm are
deposited in the conducting airways (Everard, 2001; Newman, 1985).The particulates
of size <1 µm are deposited in the alveoli region and peripheral airways (Everard,
2001). Micro-particles less than 0.5 µm are initially deposited in the human lung by
Brownian diffusion (Werner Hofmann, 2011), while larger particles are deposited by
sedimentation and inertial impaction. Breathing patterns are also responsible for
particle deposition in human airways. Due to the long residence time, slow breathing
patterns are more effective for sedimentation and Brownian diffusion, whereas a fast
breathing pattern is good for impaction (Werner Hofmann, 2011).
2.3 TARGETED DRUG DELIVERY
The lung represents an attractive alternative way of targeting drug delivery
(Kuzmov & Minko, 2015). The technology of targeted drug delivery is a significant
area of biomedicine (O. Pourmehran et al., 2015). Today, scientists and researchers
are mainly interested in recognising the role of drug particle deposition on lung
systems and their reverse impacts. This process of drug delivery can provide an
important role for researchers to assess how the particle transportation, diffusion and
deposition are completed in the specific region of the human lung. It can also provide
an advanced way of treatment for a drug particle delivery system to targeted areas
(Taherian et al., 2011). From the 1970s, when the magnetic micro-particles of
Targeting Delivery of Magnetic Aerosol Particles to Specific Regions in The Lung 13
polymer-coating were first developed, targeted drug delivery has been an interest area
for drug delivery in the lung (Pankhurst et al.). The drug particles are concentrated and
navigate towards the affected sites in the lung by using external magnetic fields.
Targeting magnetic delivery is especially attractive for chemotherapy. Drug direction
for chemotherapy through aerosol inhalation is a perfect application for targeting
magnetic drug delivery (Dikanskii, 1998).
A range of aerosolised medicines are now recommended for the use of nebulizer
systems and devices. Drug delivery through an inhalation system needs an effective
aerosolised formulation. These aerosol drug delivery devices must be used and need
to be maintained correctly by patients and caregivers. In recent years, several types of
technical developments have to led the drug delivery through the aerosol drug delivery
devices for efficient drug delivery. For example, dose tracking, materials of
manufacture, portability, breathe actuation, the patient interface, combination
therapies, and drug delivery system. These modifications have developed presentation
in all four types of devices: metered dose inhalers, spacers and holding chambers, dry
powder inhalers, and nebulisers. Furthermore, some therapies generally given by
injection are now recommended, for instance, aerosols for use in a variety of drug
delivery devices (Dolovich & Dhand, 2011).
The ability of targeted drugs to the predetermined sites is a major challenging
need for aerosol therapy (Dolovich & Dhand, 2011). There are two types of targeting
(passive and active targeting).
2.3.1 PASSIVE TARGETING
The passive targeting methodology directs deposition primarily to the
respiration, especially to the more peripheral airways and alveolar section. These
14 Chapter 3: Methodology
depositions are due to variations of droplet size of drug carrier, inhalation patterns,
breath holding for depth and duration, aerosol bolus timing to inspiratory air flow,
dosage of drug aerosol, and inhaled gas density (Dolovich et al., 2005; Heyder, 2004).
Congruently, a considerable breathe fraction in aerosol can be dropped for narrowing
at areas of respiration during exhalation, particularly when flow-restricted sections are
present (Smaldone, 2006). Oropharyngeal drug deposition can be reduced by airway
targeting, which also reduces the risk of local and systemic resulting side effects from
the absorbed dose (Brown et al., 1993; Salzman & Pyszczynski, 1988).
2.3.2 ACTIVE TARGETING
In the active targeting method, the drug deposition is completed by directing
to the infected area of the lung through the aerosol and providing a more appropriate
drug delivery to the targeted site. That means it is more active for targeted delivery
than passive targeting: for example, genes or drugs delivery directly to a lung lobe, the
Figure 2.5 Action of nanomagnetosols Mechanism (Plank, 2008).
Targeting Delivery of Magnetic Aerosol Particles to Specific Regions in The Lung 15
Aero Probe nebulising catheter of intracorporeal (TMI, London, ON, Canada) could
be inserted through a fibre optic bronchoscope into the working channel (Köping‐
Höggård et al., 2005; Selting et al., 2008). Recently, in a nebuliser solution, NPs of
super paramagnetic iron oxide are added for guiding aerosol to the affected lung region
by the influence of an external strong magnetic field (See Fig 2.5)(Dames et al., 2007).
The direct chemotherapeutic agents’ delivery to the lungs could symbolise a unique
therapeutic approach with pulmonary metastases for patients (Goel et al., 2013).
Targeted pulmonary delivery simplifies bioactive materials directly to the lung
through a controlled manner and targeted MNPs provide to the lung through an
exciting platform (Stocke et al., 2015). This is a first-line treatment for asthma, COPD,
and pulmonary infections because of its inherent advantages (Dolovich et al., 2005).
Due to pharmaceutical action, drugs will achieve more concentration and minimise
unwanted systematic side effects (Patton & Byron, 2007). Again, this inhalation
method also avoids pharmaceutical agents, which is the first pass of metabolism
(Mansour et al., 2009). For this reason, less aerosol dosage is required in this delivery
system.
Inhalation aerosol by dry powder offers many advantages, such as controllable
particle size and increased stability of formulations for targeting regions of the lung
(Carpenter et al., 1997; Dolovich et al., 2005). Also, dry powder formulations can be
used for nebulizers and pressurised meter dose inhalers (PMDIs). For all powders,
magnetic nanoparticle microcomposites (MnMs) could deposit throughout the lung if
the mass median aerosol diameter (MMAD) is < 5 μm. This inhalable treatment
presents many potential applications and targeted thermal treatment of the lung
by MNPs (Stocke et al., 2015).
16 Chapter 3: Methodology
The systematic inhalable dry powders are taken via inhaled dry powder by
pulmonary delivery to the lung (see, Fig 2.6). Again, these materials can be taken into
a capsule and placed into a dry powder inhaler for observing predictive deposition
patterns in the lung through vitro aerosol dispersion performance and also alternating
magnetic field (Stocke et al., 2015).
Recently, the advantages of pulmonary drug delivery have been growing for
treating lung diseases, especially in cystic fibrosis (CF) and lung cancer. Because of
the expanding successful aerosol formulations by the potential applications of targeted
pulmonary delivery (Stocke et al., 2015), aerosols consist of small molecule drugs and
excipients for inhalation therapies (Azarmi et al., 2008; Mansour et al., 2009).
Figure 2.6 Schematic representation of magnetic nanoparticle microcomposites
(MnMs) by pulmonary delivery (Stocke et al., 2015).
Targeting Delivery of Magnetic Aerosol Particles to Specific Regions in The Lung 17
The main advantages of an inhalation route are direct delivery of the drug by
active components in the diseased cells and organs. Also, this process can protect
possible adverse effects and potentially toxic therapeutics from other healthy organs
in the body (Fig.2.7). Though drug delivery in this way has lots of advantages, it has
also some challenges. Native nucleic acids and peptides cannot be delivered into the
lung by this drug delivery system (Kuzmov & Minko, 2015).
2.4 MAGNETIC MICRO PARTICLE TRANSPORT AND DEPOSITION
Drug delivery in the lung by aerosol inhalation is an authenticated procedure. It
has potential advantage in the treatment of respiratory disorders for drug delivery in
oral and arterial routes. The usage of inhalation aerosols allows direct achievement of
high drug concentrations for the selective treatment of the lungs (Darquenne, 2012).
The particle of one or several micrometers in size usually refers to the term
“microparticle” in drug delivery applications (Kuzmov & Minko, 2015). Many
materials composed of microparticles, including glass, ceramics, metals, and
polymers, are currently available commercially. For the drug delivery purposes, metal
Figure 2.7 Advantages and challenges of pulmonary drug delivery (Kuzmov &
Minko, 2015).
18 Chapter 3: Methodology
and polymer microparticles are being primarily used. The critical understanding of the
local and regional deposition of micro-sized aerosol is important for assessing
pulmonary health risk. It is essentially important to understand the deposition
characterisation in the targeted position of the pulmonary airways for effective
delivery of the inhaled pharmaceutical aerosol.
There are very limited studies that have been conducted for targeting magnetic
drug delivery in the specific region of the lungs. The external magnetic field as a
passive technique, which is a potential application tool of drug delivery, was adopted
by several researchers (Dahmani et al., 2009; Dolovich & Dhand, 2011; Goetz et al.,
2010; Plank, 2008). Dahmani et al., (2009) developed an aerosol cloud at the
beginning of the inspired phase for delivering aerosols to the deepest areas of the lungs
by synchronising the activation of the magnetic field with the breathing process. The
authors, however, did not show a deposition pattern for any specific lung model.
Dolovich & Dhand, (2011) have shown therapeutic applications and again, did not
consider any specific zone deposition pattern for the entire geometry. Goetz et al.,
(2010) have studied the particle size for reducing unwanted distribution outside the
target due to the impact of the magnetic force and did not consider specific areas of
the lung model for particle deposition. Plank, (2008) has developed a nano magnetic
aerosol drug targeting method for reducing undesired side effects. This study has
shown therapeutic applications and did not consider any specific zone deposition
pattern for the lung geometry. Ally et al. (2005) and Dames et al. (2007) have
developed an in vitro model to investigate the possibility of targeted magnetic aerosol
deposition for lung cancer. Dames et al., (2007) have developed nanomagnetosols for
targeting aerosol delivery to the lungs of mice. O. Pourmehran et al. (2015) have used
Lagrangian magnetic particle tracking, using a discrete phase model to investigate the
Targeting Delivery of Magnetic Aerosol Particles to Specific Regions in The Lung 19
effect of a magnetic field on behaviour of the magnetic drug career. Recently, Oveis
Pourmehran et al. (2016) have used a realistic model to investigate the human
tracheobronchial airways using computational fluid and particle dynamics. They have
developed an optimal magnetic drug characteristics coordination and magnetic impact
for drug delivery to the human lung. Based on several attempts of studying particle
deposition due to the external magnetic field effect by several authors, it is important
to investigate the particle deposition in the specific position by an external magnetic
field, by designing a more realistic drug delivery device. There are no suitable
numerical and experimental studies that have been conducted to fully understand
magnetic field effect for particle deposition in a specific targeted position.
Case study 1 (Chapter 3 and Chapter 4) of this thesis will discuss the drug
aerosols delivery on magnetic microparticle transport and deposition in the targeted
position of the human lung airways.
2.5 MAGNETIC NANOPARTICLE TRANSPORT AND DEPOSITION
Nano-particles or airborne particles are produced from nature (volcanic ash,
smoke, ocean spray, fine sand and dust etc.), the workplace (running diesel engines,
large-scale mining, and industry) and man-made processes (fires, traffic and drug
aerosols are generated by inhalers for therapeutic purposes) (Lintermann & Schröder,
2017). Moreover, the increased popularity of nanomaterial products may expose a
significant amount of NP emission into the atmosphere (Islam et al., 2017). These NPs
or drug aerosols are inhaled through the extrathoracic and tracheobronchial airways
down into the alveolar region (Zhang & Kleinstreuer, 2004). As the result of strong
diffusion and thermophoretic effects, inhaled NPs deposit into extrathoracic airways
(Bahman Asgharian & Price, 2008). A certain percentage may deposit in various lung
20 Chapter 3: Methodology
regions by touching the moist airway surfaces and hence, are accessible for
interactions with respiratory tissue (Zhang & Kleinstreuer, 2004). As a result, toxic
particles may instigate pulmonary and other diseases, while drug aerosol may be
harnessed to struggle with diseases (Zhang & Kleinstreuer, 2004). The inhalation of
drug aerosols is broadly used for the treatment of lung disorders such as COPD,
asthma, respiratory infection, CF and more recently, lung cancer. NPs significantly
influence their retention for shape and size in the lungs and targeting properties. At
present, for drug delivery purposes, NPs are widely used through various delivery
routes, including inhalation. Targeted NP delivery to the affected lung tissue may
improve therapeutic efficiency and minimise unwanted side effects (Dames et al.,
2007). Despite these attractive advantages, systemic inhalation of therapeutic drug
aerosol delivery in the specific region of the lung is still not clear (Kuzmov & Minko,
2015). A comprehensive investigation of MNPs TD in a lung model is essential for the
understanding of pharmaceutical aerosol transport into the targeted position of the
lung.
A wide range of studies has been conducted on MNPs TD for targeted drug
delivery to diminish the diseased cells (Ally et al., 2005; Arruebo et al., 2007;
Chomoucka et al., 2010; Cregg et al., 2008; Fernández-Pacheco et al., 2007; A. Kumar
et al., 2010; Lin et al., 2009; Mishra et al., 2010; Shubayev et al., 2009; Stepp &
Thomas, 2009; Sun et al., 2008).
There are limited studies that have been conducted on MNPs for targeting
magnetic drug delivery in the specific region of lungs. Dames et al. (2007) developed
superparamagnetic iron oxide nanoparticles (nanomagnetosols) in a combination of
target-directed magnetic gradient fields for targeting aerosol delivery to the lungs of
mice. The theoretical and experimental study concluded that the nanomagnetosols may
Targeting Delivery of Magnetic Aerosol Particles to Specific Regions in The Lung 21
be useful for treating localised lung disease. D. Bennett William et al. (2004)
discussed the potential application of aerosol drug delivery and deposition techniques
for both serial and parallel pathways in the lung. They concluded that aerosol bolus
delivery and extremely slow inhalation of aerosols in diagnostic lung tests may be
useful for targeting drug delivery to the conducting airways. Ally et al. (2005)
developed an in vitro model to investigate the possibility of targeted magnetic aerosol
deposition for lung cancer and to predict the trajectories of the aerosol particles. They
concluded that aerosol particle concentration and magnetic field gradient are important
considerations for targeting magnetic delivery of aerosols. Mishra et al. (2010) focused
on the potential application of nanotechnology in medicine and discussed drug-
delivery systems as well as their applications in therapeutics, imaging and diagnostics.
They concluded that the surface characteristics of NPs and a better understanding NPs
in vivo behaviour can achieve successful development on targeted NPs for use in
therapy and imaging. Wilczewska et al. (2012) investigated the nano carrier
connections with drugs and magnetic nanoparticles as carriers in drug delivery systems
(DDS). They concluded that for the drug delivery systems, nanocarriers can improve
the therapeutic and pharmacological properties of conventional drugs. Lübbe et al.
(2001) reported that magnetic drug targeting is one of the various possibilities of drug
targeting, and site-directed drug targeting is one way of local or regional antitumor
treatment. Sharma et al. (2015) studied magnetic nanoparticle transport in a channel
for targeted drug delivery. They concluded that the fluid velocity and MNPs is
decreasing with the increasing of a magnetic field. Roa et al. (2011) showed that
inhalable doxorubicin NPs are an effective way to treat lung cancer. They concluded
that a non-invasive route of administration might change the way lung cancer is treated
in the future. O. Pourmehran et al. (2015) have used Lagrangian magnetic particle
22 Chapter 3: Methodology
tracking using a discrete phase model to investigate the effect of a magnetic field on
the behaviour of the magnetic drug carrier. Recently, Oveis Pourmehran et al. (2016)
have used a realistic model to investigate the human tracheobronchial airways using
computational fluid and particle dynamics. They have developed an optimal magnetic
drug characteristics coordination and magnetic impact for drug delivery to the human
lung.
Until now there have been no numerical or analytical studies that consider the
human respiratory tract, available in the literature on magnetic nanoparticles TD for
targeting drug delivery in the specific region of the human lung. Hence, detailed
analysis of the MNPs transport and deposition in the human respiratory tract are
needed for a better understanding of the fluid-particle dynamics.
Case study 2 (Chapter 3 and Chapter 4) of this thesis will discuss the magnetic
nano-particle deposition in the targeted lung region.
2.6 SUMMARY AND IMPLICATIONS
Respiratory health risk is essentially increasing, as particulate emission is
increasing day by day. Inhaled detrimental particulate matter deposited in the airways
has been implicated in a causal connection with a large spectrum of respiratory
diseases. The aerosol particulates occur different respiratory diseases by producing
inflammation in the lung epithelium cells. Based on the estimation presented in
(Saillaja AK, 2014), asthma affects 300 million people in the world, and more than 22
million in the United States alone. In 2017, lung cancer was the most common cause
of cancer death for men and women in Australia (12,434 deaths overall: 7,094 in men;
5,340 in women), accounting for 18.9 per cent of all cancer deaths ("Australian
Government. Lung cancer statistices. Retrieved August 8, 2017, from https://lung-
Targeting Delivery of Magnetic Aerosol Particles to Specific Regions in The Lung 23
cancer.canceraustralia.gov.au/statistics.,"). In the case of traditional drug delivery
devices, a significant amount of therapeutic particles are deposited at an unwanted
position of the lung and generate different types of side effects. That is why it is
essential to develop a more accurate and efficient drug delivery device for the targeted
drug delivery system. The proper understanding of the respiratory air flow field
characterisation, targeted magnetic particle transport and deposition, is important for
better delivery of drug aerosols in the specific pulmonary health burden assessment. It
is clear from the literature review that the study of particle deposition in the human
respiratory tract is vitally important for developing effective drug treatment methods
for respiratory diseases. Particle deposition in the human lung is an important field for
researchers. The numerical modelling of nano and micro particle deposition in a
patient-specific way in the human lung is very important for the improvement of drug
treatment methods. The investigation of magnetic aerosol drug deposition under the
influence of an external magnetic field will be an excellent effort for the future advance
of research on drug delivery in the human lung. Because of the complex geometrical
structure of the human bronchial tree, the deposition pattern depends considerably on
magnetic source position, magnetic number, particles diameter, inhalation condition
and magnetic field strength. The MNPS and micro-particle deposition in the specific
region of human lung under an external magnetic field is an area with limited
investigation area. A comprehensive magnetic particle TD analysis in the specific
region of lung airways is important in order to increase the efficiency of the targeted
drug delivery and minimise unwanted side effects.
24 Chapter 3: Methodology
Chapter 3 : METHODOLOGY
In order to achieve the ultimate aims and objectives of this research, a theoretical
frame-work, as well as software simulation work, has been performed. The main
challenge in conducting the proposed work is geometry generation. Firstly, the 3-D
lung geometry is generated by geometry generation software. Then the computational
mesh of the human bronchial tree is generated by using commercial software ANSYS
18. ANSYS FLUENT 18 is used to solve the Navier-Stokes equations for
incompressible airflow with appropriate boundary conditions. For this present study,
the particles are considered smooth surface micro-particles and NPs, which have
magnetic susceptibility. After solving the governing equation by a simple algorithm,
these magnetic particles have been injected in a steady state manner. The desired
external magnetic force has been applied by a Magneto hydro-dynamics (MHD) model
and programmed based depending on particle position. The complete step-by-step
methodology of the present work is given below:
Targeting Delivery of Magnetic Aerosol Particles to Specific Regions in The Lung 25
Figure 3.1: Framework of the present thesis.
Figure 3.1 presents the detailed framework of the present study. The present
thesis lung model is developed from solid works. An ANSYS 18.0 meshing module is
used for advanced and high quality mesh generation. K- 𝜔 low Reynolds number
model, Euler-Lagrange (E-L) based discrete phase model (DPM) and MHD are used
for the shape- and size- specific magnetic particle transport and deposition in the
specific region of the lung. MATLAB and Tecplot 360 software are used for post-
processing.
26 Chapter 3: Methodology
3.1 ASSUMPTIONS FOR NUMERICAL SIMULATIONS
The present numerical study assumes the following assumptions for targeted
magnetic particle transport and deposition in the specific region of the human lung:
i) Velocity inlet and pressure outlet boundary conditions are assumed for this
study. 7.5 litre per minute (lpm), 9 lpm, 15 lpm, 30 lpm and 60 lpm flow
rates are used to simulate different human physical activity conditions for
targeted drug delivery. Zero pressure is used at all outlets of the 2-
generation symmetric model. The present study used the first targeted
magnetic drug delivery in the specific region of the human lung for a 2-
generation symmetric model.
ii) Magnetic number or intensity is assumed for this study. External magnetic
fields of 0.181 tesla, 1.5 tesla, 2.5 tesla, and 3 tesla are used to simulate
different intensity of magnetic conditions for targeted drug aerosol delivery
in the specific position of the lung.
iii) The present study considers different shapes and sizes of particle diameter;
2 μm, 4 μm, 6 μm, 1-nm, 10-nm, 50-nm, 100-nm and 500-nm are used to
simulate different effects of magnetic particle transport and deposition in
the specific position of the lung by external magnetic field.
iv) The present study considers only one-way inhalation effects on magnetic
aerosols’ particle transport and deposition. The simulations run until every
particle has either escaped or is trapped through the outlets.
v) The present study used the boundary condition as a ‘trap’, which means the
particle will be deposited if the particles touches the wall. Once the particle
touches the airway wall, simulation will store the information (position,
Targeting Delivery of Magnetic Aerosol Particles to Specific Regions in The Lung 27
velocity, etc.) of those particles, and the trajectory calculations are
terminated.
vi) Two different magnetic field positions are used to show the deposition
enhancement in the specific position of the human lung.
vii) Stokes-Cunningham correction law is used for the targeted magnetic nano-
particle modelling. Specific correction factor values are used for the
different diameter particles.
3.2 NUMERICAL METHODOLOGY FOR CASE STUDY 1
ANSYS (Fluent) 18.0 was used to solve the following governing equations with
proper initial and boundary conditions. The steady-state flow field is converged when
the residuals decreased to less than10−6. Air was considered as the working fluid with
constant density (ρ), viscosity (μ) and fluid static pressure (p). The governing
equations for continuity and momentum equations are given as:
Continuity equation:
𝜕𝑢𝑖
𝜕𝑥𝑖= 0 (3.1)
Momentum equations:
𝜕𝑢𝑖
𝜕𝑡+ 𝑢𝑗
𝜕𝑢𝑖
𝜕𝑥𝑗= −
1
𝜌𝑓
𝜕𝑝
𝜕𝑥𝑖+
𝜕
𝜕𝑥𝑗[(𝑣𝑓 + 𝑣𝑇) (
𝜕𝑢𝑖
𝜕𝑥𝑗+
𝜕𝑢𝑗
𝜕𝑥𝑖)]
(3.2)
Where 𝑢𝑖 and 𝑢𝑗 (i, j = 1, 2, 3) are the velocity components along x-, y- and z-
directions. Steady k–ω low Reynolds number turbulence model was adopted to
calculate the air flow in the present study. The SIMPLE algorithm was used for the
pressure-velocity coupling. The second-order upwind numerical scheme was chosen
to discretise different terms in the transport equations. The k–ω turbulence model
governing equations are written as follows:
28 Chapter 3: Methodology
𝜕𝑘
𝜕𝑡+ 𝑢𝑗
𝜕𝑘
𝜕𝑥𝑗= 𝑃 − 𝛽∗𝜔𝑘 +
𝜕
𝜕𝑥𝑗[(𝑣𝑓 + 𝛼𝑘𝛼∗ 𝑘
𝜔)
𝜕𝑘
𝜕𝑥𝑗]
(3.3)
with Pseudo vorticity equation:
𝜕𝜔
𝜕𝑡+ 𝑢𝑗
𝜕𝜔
𝜕𝑥𝑗=
𝛾𝜔
𝑘𝑃 − 𝛽𝜔2 +
𝜕
𝜕𝑥𝑗[(𝑣𝑓 + 𝛼𝜔𝛼∗
𝑘
𝜔)
𝜕𝜔
𝜕𝑥𝑗] +
𝛼𝑑
𝜔
𝜕𝑘
𝜕𝑥𝑗
𝜕𝜔
𝜕𝑥𝑗
(3.4)
where the turbulent viscosity, 𝑣𝑇 = 𝐶𝜇𝑓𝜇𝑘
𝜔 , and the function, 𝑓𝑢 is defined as 𝑓𝑢 =
exp [−3.4
(1+𝑅𝑇50
)2] with 𝑅𝑇 =
𝜌𝑘
(𝜇𝜔) . The other coefficients in the above equations are
chosen from (Oveis Pourmehran et al., 2016) :
𝑅𝛽 = 8, 𝑅𝜔 = 2.61, 𝑅𝑘 = 6, 𝛼0 =1
9 , 𝛽0 = 0.0708 , 𝛽0
∗ = 0.09 , 𝛼∞∗ = 1,
𝜎𝜔 = 𝛼𝑘 = 0.5
Wall condition is considered as trap (if the particle trajectory touch the wall then the
trajectory calculations will be terminated and the fate of the particle is recorded as
trapped), outlet condition is pressure outlet and inlet is uniform mass flow considered
for the boundary conditions.
To simulate the particle trajectories, the Lagrangian particle tracking approach and
discrete phase model (DPM) have been applied. In this approach, the force balance
equation for individual particles is given as follows:
�� = 𝐹𝐷 + 𝐹𝑀
= 𝑚𝑝.𝑑𝑈𝑝
𝑑𝑡
(3.5)
where 𝑈𝑝 is the particle velocity and 𝐹 is the force term. 𝐹𝐷
, 𝐹𝑀 are drag and magnetic
forces, respectively.
3.2.1 DRAG FORCE
For a spherical particulate, the Stokes drag force is expressed as:
Targeting Delivery of Magnetic Aerosol Particles to Specific Regions in The Lung 29
𝐹𝐷 =
18𝜇
𝜌𝑝𝑑𝑝2
𝑚𝑝𝑓𝑅𝑒𝑃
24(𝑢𝑓 − 𝑢𝑝) (3.6)
The drag coefficient 𝐶𝐷 , for smooth particle using the spherical drag law can be taken
from
𝑓 = 𝑎1 +𝑎2
𝑅𝑒𝑃+
𝑎3
𝑅𝑒𝑃2 (3.7)
where 𝑅𝑒𝑃 is the particle Reynolds number, which is defined as 𝑅𝑒𝑃 ≡𝜌𝑓𝑑𝑃|𝑢𝑃−𝑢𝑓|
𝜇𝑓 .
𝑢𝑃, 𝜌𝑓 , 𝜌𝑃 𝜇𝑓 , 𝑢𝑓 and 𝑑𝑃 are the air velocity, fluid density, particle density, particle
velocity, fluid molecular viscosity and particle diameter. Also in (3.7) 𝑎1, 𝑎2 and 𝑎3
are constants.
3.2.2 MAGNETIC FORCE
For magnetic force, the Magneto Hydrodynamics Model (MHD) approach has
been applied. The fluid flow field and the magnetic field connection can be implicit on
the basis of induction of electric current due to the movement of conducting material
in a magnetic field and the effect of Lorentz force as the result of electric current and
magnetic field interaction. This equation provides the connection between the flow
and the magnetic field.
Electromagnetic fields are determined by Maxwell’s equations:
∇ ∙ �� = 0 (3.8)
∇ × �� = −𝜕��
𝜕𝑡 (3.9)
∇ ∙ �� = 𝑞 (3.10)
∇ × �� = 𝐽 +𝜕𝑗
𝜕𝑡 (3.11)
30 Chapter 3: Methodology
The magnetic simulation equation can be derived from Ohm’s law and Maxwell’s
equation, which is:
𝜕��
𝜕𝑡+ (𝑈. ∇)�� =
1
𝜇𝜎∇2�� + (��. ∇)𝑈
(3.12)
From Ampere’s relation the current density, 𝐽 can be calculated as:
𝐽 =1
𝜇∇ × �� (3.13)
Generally, the magnetic field, �� ( �� = 𝜇0𝐻) in an MHD problem can be decomposed
into the externally imposed field, 𝐵0 and the induced field, �� due to fluid motion. Only
the induced field, �� must be solved.
From Maxwell’s equations, the imposed field, 𝐵0 satisfies the following equation:
∇2𝐵0 −
𝜇𝜎(𝜕𝐵0 )
𝜕𝑡= 0
(3.14)
3.2.2.1 EXTERNALLY IMPOSED MAGNETIC FIELD GENERATED IN NON-
CONDUCTING MEDIA
In this case, the imposed field 𝐵0 satisfies the following conditions:
∇ × ��0 = 0 (3.15)
∇2��0 = 0 (3.16)
With �� = 𝐵0 + ��, the induction equation (3.14) can be written as:
𝜕��
𝜕𝑡+ (𝑈. ∇)�� =
1
𝜇𝜎∇2�� + ((𝐵0
+ ��). ∇) 𝑈 − (��. ∇)𝐵0 −
𝜕𝐵0
𝜕𝑡
(3.17)
The current density is:
Targeting Delivery of Magnetic Aerosol Particles to Specific Regions in The Lung 31
𝑗 =1
𝜇∇ × �� = 0 (3.18)
3.3 NUMERICAL METHODOLOGY FOR CASE STUDY 2
A Lagrangian particle-tracking scheme and an ANSYS 18.0 (FLUENT) solver
based DPM and MHD model have been applied to investigate the nano-particle
Transport and Deposition in the 2-generation airways. Euler-Euler (E-E) and Euler-
Lagrange (E-L) approaches are usually used for nanoparticle simulation. An E-L
approach solves the particle trajectory equation while an E-E approach is used to solve
convection-diffusion equations (Islam et al., 2017). The E-L method tracks the
individual particle trajectory by considering inertia, electrostatic effects, diffusivity,
and near wall terms directly (Longest et al., 2004). The present study uses the E-L
approach as it also considers dp ≥ 100 nm.
The present study considers the 2-generation lung model as derived from the
trachea, which does not include the extrathoracic region. The k- low Reynolds
number turbulence model is used for the current study and calculated maximum
Reynolds number is 5×103. Reynolds number describes the ratio of the magnitudes of
the inertial and viscous forces on the particle.
The k–ω turbulence model governing equations are written as follows:
𝜕𝑘
𝜕𝑡+ 𝑢𝑗
𝜕𝑘
𝜕𝑥𝑗= 𝑃 − 𝛽∗𝜔𝑘 +
𝜕
𝜕𝑥𝑗[(𝑣𝑓 + 𝛼𝑘𝛼∗ 𝑘
𝜔)
𝜕𝑘
𝜕𝑥𝑗]
(3.19)
Pseudo vorticity equation:
𝜕𝜔
𝜕𝑡+ 𝑢𝑗
𝜕𝜔
𝜕𝑥𝑗=
𝛾𝜔
𝑘𝑃 − 𝛽𝜔2 +
𝜕
𝜕𝑥𝑗[(𝑣𝑓 + 𝛼𝜔𝛼∗
𝑘
𝜔)
𝜕𝜔
𝜕𝑥𝑗] +
𝛼𝑑
𝜔
𝜕𝑘
𝜕𝑥𝑗
𝜕𝜔
𝜕𝑥𝑗
(3.20)
32 Chapter 3: Methodology
Where j
iij
x
uP
; ijij
k
kijij
x
uST
3
2)
3
22(
;
i
j
j
iij
x
u
x
uS
2
1 ;
f0 ; the turbulent viscosity, 𝑣𝑇 = 𝐶𝜇𝑓𝜇𝑘
𝜔 and the function, 𝑓𝑢 is defined as 𝑓𝑢 =
exp [−3.4
(1+𝑅𝑇50
)2] with 𝑅𝑇 =
𝜌𝑘
(𝜇𝜔) . The other coefficients in the above equations are
chosen from ANSYS fluent 18.0:
𝑅𝛽 = 8, 𝑅𝜔 = 2.95, 𝑅𝑘 = 6, 𝛼0 =1
9 , 𝛽0 = 0.0708 , 𝛽0
∗ = 0.09 , 𝛼∞∗ = 1, 𝜎𝜔 = 𝛼𝑘
= 0.5
Wall condition, pressure outlet and velocity condition were used for the boundary
conditions.
In this approach, the force balance equation for individual particles is given as follows:
�� = 𝐹𝐷 + 𝐹𝑀
= 𝑚𝑝.𝑑𝑈𝑝
𝑑𝑡
(3.21)
where 𝑈𝑝 is the particle velocity and 𝐹 is the force term. 𝐹𝐷
, 𝐹𝑀 are drag and
magnetic forces respectively.
The following mass and momentum equations respectively were solved to calculate
air flow.
mSt
v
(3.22)
where Sm is the mass source term.
FgITpt
vvv vvv
3
2
(3.23)
Targeting Delivery of Magnetic Aerosol Particles to Specific Regions in The Lung 33
where, p is fluid static pressure, g
is body force due to gravity, μ is the molecular
viscosity, I is the unit tensor, and F is body force due to external force (particle-fluid
interaction). A pressure-velocity coupling scheme, SIMPLE, was used to solve the
pressure-velocity coupling in the flow field. A parabolic inlet condition for laminar
flow (White, 2003) was used
)1(2)(2
2
R
ruru av
(3.24)
where R is the airway inlet radius.
Brownian motion was considered for this nano-particle simulation. An appropriate
particle motion equation was solved to calculate the individual particles.
( )p
p gg p iD i i Brownian Lift i
p
duF u u F F g
dt
(3.25)
For a spherical particulate, the Stokes -Cunningham drag force is expressed as:
cpp
g
DCd
F2
18
(3.26)
)4.0257.1(2
1 2/1.1
pd
p
c ed
C
(3.27)
Where cC is the Cunningham correction factor. The specific correction factor values
were used for different diameter particles. 𝜌𝑃 , 𝑑𝑃, are particle density, particle
diameter and λ is the mean free path of the gas molecules. The Brownian force
amplitude is defined as
t
SFBrownian
0
(3.28)
34 Chapter 3: Methodology
Where ζ is the unit variance independent Gaussian random number, ∆t is the particle
time-step integration, and S0 is the spectral intensity. S0 is defined as
c
g
p
pp
Bo
Cd
TkS
252 )(
216
(3.29)
T is the fluid absolute temperature, kB is the Boltzmann constant, ρg is the gas density.
The Saffman’s lift force is used (A. Li & Ahmadi, 1992), which is a generalisation of
the Saffman expression (Saffman, 1965).
)()(
2
4/1
2/1
p
kllkpp
ij
Lift uuddd
dKvF
(3.30)
where K=2.594 1and ijd is the deformation tensor.
For magnetic force, the Magneto hydrodynamics model (MHD) approach has been
applied. The magnetic simulation equation is derived from Ohm’s law and Maxwell’s
equation. This equation provides the connection between the flow and the magnetic
field.
The magnetic force, 𝐹𝑀 on a small sphere in a nonmagnetic fluid, was calculated as
��𝑀 =1
2𝜇0χ𝑉𝑃∇ (𝐻2 ) (3.31)
Where 𝜇0 is the magnetic permeability of vacuum, χ is the magnetic susceptibility of
the particle, Vp is the particle volume, and 𝐻 is the magnetic field intensity.
The magnetic susceptibility of the particle equation (Oveis Pourmehran et al., 2016)
is defined as:
χ = −0.14𝑑𝑝. 106 + 0.98 (3.32)
Where, 𝑑𝑝 is the particle diameter.
Targeting Delivery of Magnetic Aerosol Particles to Specific Regions in The Lung 35
Magnetic number Mn (Tesla) is defined as follows (Oveis Pourmehran et al., 2016):
𝑀𝑛 = 𝜇0𝐻0 (3.33)
𝐻0 is the characteristic magnetic field strength. Magnetic number is dependent to the
magnetic field intensity.
36 Chapter 4: Results and Discussion
Chapter 4 : RESULTS AND DISCUSSION
The purpose of this chapter is to interpret and describe the significance of case
study findings for the present thesis. The present thesis case study includes the
discussion of aerosolised magnetic microparticle (Case study 1) and magnetic
nanoparticle (Case study 2) transport and deposition in the targeted position of the
human lung.
4.1 CASE STUDY 1: MAGNETIC MICROPARTICLE
4.1.1 COMPUTATIONAL DOMAIN AND MESH GENERATION
The 2-generation lung symmetric model is constructed to calculate the complex
flow field in the human lung for k- low Reynolds number turbulence model. This 2-
generation lung geometry contains 450,429 elements and 179,660 nodes.
Targeting Delivery of Magnetic Aerosol Particles to Specific Regions in The Lung 37
(a)
(b)
(c)
Figure 4.1 (a) Anterior view of the 2-generation mesh with 179,660 unstructured
cells, (b) first bifurcation, (c) inlet mesh, (d) inflation layer mesh near to the wall, (e)
terminal bronchioles mesh, (f) outlet mesh of 2 generation lung model.
(f)
(e)
(d)
38 Chapter 4: Results and Discussion
An unstructured fine boundary layer mesh is constructed to calculate the
complex flow field (Fig 4.1 (a)). Fig 4.1 (b) shows the mesh for the first bifurcation of
a 2- generation lung model. An inflation of 10 boundary layer mesh was calculated
near the solid wall (Fig 4.1(c)). Fig 4.1 (d) shows the inflation layer mesh of 2-
generation lung model. Fig 4.1 (e) shows the outlet mesh of a 2- generation lung
symmetric model.
4.1.2 GRID INDEPENDENCE TEST
After completing the meshing, a grid resolution test is performed for choosing
the appropriate mesh for the present simulation. Since the fluid flow is complex and
results are sensitive due to regional turbulence effects, it is required to consider a grid
resolution to adequately refine the mesh. This model is tested for seven different grid
numbers (see Fig. 4.2), comparing with the maximum velocity calculated on the outlet
plane. The flow seems converged from the red point and it is conceivable to use any
of the grid numbers from this point. However, 179,660 grid numbers are adopted for
the present simulations. Note that the minimum and the maximum cell sizes are 1.e-
005 m and 1.9772e-003m respectively. Also, an inflation of 10 boundary layer is
chosen in the boundary layer (near the solid wall).
Targeting Delivery of Magnetic Aerosol Particles to Specific Regions in The Lung 39
4.1.3 MODEL VALIDATION
A comprehensive validation has been performed for the present study. The
present micro-particle simulation results have been compared with the experimental
data sets of steady laminar flows available in the literature.
For the present airway model, results are compared with the observations by (Cheng
et al., 2010) and (Kleinstreuer et al., 2008) for three inhalation flow rates (Fig.4.3).
The overall deposition fraction (DF) is compared against the Stokes number. The
Stokes number is defined by 𝑠𝑡 = 𝜌𝑝𝑑𝑝2𝑈/(9𝜇𝐷), where U is the mean velocity and
D is the minimum hydraulic diameter. All experimental results show that the DF is
proportional to the Stokes number. The experimental data and the present numerical
result show the similar trend against total deposition for the Stokes number. However,
the DF of the present model is slightly lower than that of the experimental model, as
the present model has considered only two generations instead of the four generations
that were considered by the experimental study.
0
1
2
3
4
5
6
7
8
9
10
0 50000 100000 150000 200000 250000 300000
Max
imu
m v
elo
city
(m
/s)
Grid Number or nodes
Figure 4.2 Maximum velocity grid convergence
40 Chapter 4: Results and Discussion
Figure 4.3 Present simulated particle deposition efficiency comparison with the
experimental data of (Cheng et al., 2010) and (Kleinstreuer et al., 2008).
Figure 4.4 Particle deposition fraction comparison between the present simulation
data with the experimental different data sets of (Kleinstreuer et al., 2008), Chen et
al.,(1999), (Lippmann & Albert, 1969), (Chan & Lippmann, 1980), Foord et al.,
(1978), (Stahlhofen et al., 1980) , Stahlhofen et al., (1983), (Emmett et al., 1982) and
(Bowes & Swift, 1989).
Targeting Delivery of Magnetic Aerosol Particles to Specific Regions in The Lung 41
Fig 4.4 shows the present airway model results compared with the observations of
(Kleinstreuer et al., 2008), Chen et al.,(1999), (Lippmann & Albert, 1969), (Chan &
Lippmann, 1980), Foord et al., (1978), (Stahlhofen et al., 1980) , Stahlhofen et al.,
(1983), (Emmett et al., 1982) and (Bowes & Swift, 1989) for impaction parameter.
This result shows the comparison of microparticle deposition fraction in the present
airway model with in vivo deposition data as a function of the impaction parameter.
The impaction parameter is defined by 𝑑𝑎𝑒2 𝑄(𝜇𝑚2𝐿𝑚𝑖𝑛−1), where 𝑑𝑎𝑒 is the
aerodynamic particle diameter and Q is the flow rate. All experimental results show
that the DF is proportional to the impaction parameter. The experimental data and the
present numerical result show the similar trend for the impaction parameter. The
present micro particle DF for impaction parameter shows good agreement with the
experimental data, but the trend is slightly lower than the experimental data as they
have used a 4- generation lung model in their experiment and a 2-generation lung
model has been chosen for the present simulation.
Figure 4.5 Geometry specification. (Magnet position 2 has been set on the left lung)
42 Chapter 4: Results and Discussion
The 2- generation lung model specification and magnetic source position has been
indicated in Fig 4.5. Position 1 and position 2 indicate the magnetic field position.
Position 2 has been set on the left lung (targeted region). Due to the symmetrical shape
of the present model, inlet and outlet are same. Right and left generation of this model
are indicated by rg2 and lg2.
Fig 4.6 shows particle deposition efficiency comparison based on magnet position
between the present simulation and the experimental data of Cohen, (2009), Haverkort,
(2008), and Pourmehran et al., (2016). The total deposition efficiency under an
externally applied magnetic force for the present model is in the range of the
experimental data and sufficiently reaches an agreement with the published literature.
Figure 4.6 Particle deposition efficiency using magnetic position comparison
between the present simulation and experimental data sets of (Cohen, 2009),
(Haverkort, 2008), and (Oveis Pourmehran et al., 2016)
Targeting Delivery of Magnetic Aerosol Particles to Specific Regions in The Lung 43
4.1.4 POST PROCESSING RESULTS FOR MAGNETIC MICRO-PARTICLE
The present 2- generation lung airway model has been designed to determine the
exact deposition in the targeted region. Fig 4.7 (a) shows the velocity magnitude for
triple bifurcation lung airways.
The velocity magnitude at different outlets of the double bifurcation model is
investigated and is shown in Fig. 4.7. Figs. 4.7(b, c) show the velocity contour at the
(a)
(b) (c)
(d) (e)
Figure 4.7 Velocity profiles in the symmetric bifurcation airway model for steady
inhalation with Q= 60 lpm. (a) Contour of velocity magnitude for (a) 2- generation lung
model; (b ) Left outlet 1and (c) Left outlet 2; (d) Right outlet 1and (e) Right outlet 2.
44 Chapter 4: Results and Discussion
outlet planes of the left lung, whereas the velocity contour at the outlet planes of the
right lung are presented in Figs. 4.7(d, e). The overall flow contour shows a vortex is
generated due to the strong change of the airway cross-sectional area. However, the
turbulence intensity at the left outlet 2 and right outlet 1 seems stronger than the other
outlets. The highly complicated airway bifurcation, change of the angle and curvature,
and centrifugally-induced pressure stimulates the velocity field at the selected outlet
planes of the airway model.
Magnitude of B Magnitude of B
(a) (b)
Figure 4.8: Contour of Magnetic source for Mn=2.5T (a) position 1; (b) position 2.
Particle traces coloured by particle residence time for (c) Position 1; (d) Position
2.
(c) (c)
(d)
Targeting Delivery of Magnetic Aerosol Particles to Specific Regions in The Lung 45
Figs.4.8 (a, b) clarify the effect of magnetic intensity at two targeted positions. To
identify the magnetic source intensity, the magnitude of �� (magnetic flux density) is
shown for position 1 and position 2. It is found that the magnetic field intensity is
higher in wall position 1 (targeted position) than other positions in the lung airways
when the magnetic source is in position 1, as shown in Fig.4.8 (a). Correspondingly,
in Fig.4.8 (b), magnetic field intensity is higher in the wall at position 2 (targeted
position) when the magnetic source is in position 2. Due to the maximum intensity of
magnetic flux on the two specific targeted positions, the present result shows the DE
have been increased on those two positions. Magnetic flux density (��) diminishes with
the increasing of distance from the magnetic source position. Figs.4.8 (a, b) have been
shown to investigate where the magnetic field intensity is maximum after applying a
magnetic field. To show how particles interact in the presence of this magnetic field,
particle traces are shown in terms of particle residence time in Figs.4.8(c, d) after
creating magnetic fields in two different position. Figs.4.8(c, d) show the maximum
number of trajectories for a particle hitting a given targeted location and the deposition
particle is higher on that position.
46 Chapter 4: Results and Discussion
Fig.4.9 shows the contour of turbulence kinetic energy (TKE) magnitude for two
different magnetic source positions in the present model. Fig.4.9 (a) shows the
magnitude of TKE contour in the targeted magnetic field position 2. Similarly Fig.4.9
(b) shows the TKE contour magnitude for magnetic field position 1. In turbulent flow,
the fluid speed at a point is continuously undergoing changes in both direction and
magnitude. Turbulent intensity is measured by TKE. It is recognised that for
Turbulent Kinetic Energy Turbulent Kinetic Energy
(b)
(a) (b)
Figure 4.9 Turbulent kinetic energy of magnitude contour for (a) position 2; (b) position
1; Particle traces coloured by (c) velocity magnitude for position 1; (d) velocity
magnitude for position 2.
(c) (d)
Targeting Delivery of Magnetic Aerosol Particles to Specific Regions in The Lung 47
turbulence kinetic energy, airflow rapidly goes faster in the compression region and as
a result, a maximum number of particles are deposited on that region. Fig.4.9(c) shows
the velocity magnitude for magnetic particle for position 1. Fig .4.9(d) shows the
velocity magnitude for magnetic particle for position 2. Velocity is a vector quantity.
The change of particle position over the injected time and particle direction movement
is identified by velocity magnitude.
(a) (b)
(c)
(d)
Figure 4.10 Effect of flow rates on particle transport outline and DE (%) for Position
2, 𝑑𝑝 = 4 𝜇𝑚, 𝑀𝑛 = 2.5 𝑇, (a) 15 lpm; (b) 30 lpm; (c) 60 lpm; (d) Total deposition
efficiency in terms of flow rates.
48 Chapter 4: Results and Discussion
Figs.4.10 (a, b, c) represent the deposition efficiency for three different breathing flow
rates (slow, medium and fast) i.e., 15 lpm, 30 lpm and 60 lpm respectively when the
magnetic number, 𝑀𝑛 = 2.5 T, magnetic source position is in position 2 and the
particle diameter is 4 𝜇𝑚. At slow breathing condition (15 lpm), microparticle
deposition at the targeted position is significantly increased more than any other
region, as shown in Fig.4.10 (a). At slow breathing condition, the total percentage of
deposition is 27.06 and at the targeted position it is 23.84. At 30 lpm, which represents
a medium breathing pattern, the majority of 4𝜇𝑚 diameter particles are deposited in
the left lung in Fig. 4.10(b). The percentage of overall deposition for a medium
breathing condition is 42.92, where in left lung it is 36.55. At 60 lpm, which depicts a
fast breathing pattern, the maximum number of particles deposited in the targeted
region i.e., wall position 2 as well as the deposition concentration is significantly
higher than other flow rates considered here, as shown in Fig.4.10(c). The percentage
of overall deposition for fast breathing condition is 76.69 where in the targeted
position, the percentage is 36.30 and in the left lung, it is 30.49. During the slow
breathing pattern, a fewer number of particles are deposited; the number of deposited
particles increases noticeably with the increase of flow rate. It is also observed that
some particles have deposited at the carinal angle of the first bifurcation. The
microparticle inertia plays a vital role to deposit particles at the carinal angle. A lesser
number of 4 µm particles are deposited at the first bifurcation, at the slow breathing
pattern. The number of deposited particles at the carinal angle increases noticeably
with the increase of flow rate. Fig. 4.10(d) shows the overall deposition efficiency for
three different flow rates. The reason for these types of DE pattern is higher flow rates.
Targeting Delivery of Magnetic Aerosol Particles to Specific Regions in The Lung 49
Figure 4.11 Particle diameter effect on particle transport outline and DE (%) for
position 2, 𝑀𝑛 = 2.5 𝑇, Q=60 lpm (a) 𝑑𝑝 = 2 𝜇𝑚; (b) 𝑑𝑝 = 4 𝜇𝑚; (c) 𝑑𝑝 = 6 𝜇𝑚;
(d) overall deposition efficiency.
To investigate the deposition on a targeted region for different particle sizes, three
different sizes of particles, 2 𝜇𝑚, 4𝜇𝑚, and 6 𝜇𝑚 are considered in Fig.4.11 for
(d)
(a) (b)
(c)
50 Chapter 4: Results and Discussion
Mn=2.5T, position 2, and Q=60 lpm. The deposition scenario evidently indicates that
a significantly larger number of 2 μm diameter particles are deposited in the targeted
lung region than any other region, compared to the 4 µm and 6 µm diameter particles.
Smaller diameter particles reach the targeted region by external magnetic field
intensity due to lower inertia, despite fast flow rates. The total percentage of deposition
for 2 μm particles is 38.45 whereas, at the targeted position, deposition percentage is
12.33 and for the targeted left lung it is 25.01 in Fig 4.11(a). Fig.4.11 (b) shows the
deposition scenario for 4 µm particles. For 4 µm particle diameter, the overall
deposition percentage is 47.396, whereas, at the targeted position, it is 36.30. The
deposition pattern for 6 μm is shown in Fig.4.11(c) and the overall deposition
percentage for 6 μm is 64.03 and targeted position percentage is 20.11. It is clear that
the influence of the magnetic field on the magnetic drug carrier for 𝑑𝑝 = 4 μm is more
noticeable in the target position than for other particle sizes, as is shown in Fig.4.11c.
Fig.4.11 (d) shows the overall deposition concentration is higher at large particle size.
Due to the inertial impaction of particles, it is expected that by increasing the particle
diameter, the DE will be higher, which satisfies the present study desire. It is also
observed that the DE is higher in targeted position 2 (left branch) than the other areas
of the present lung model, which satisfies the aim of the present study.
Targeting Delivery of Magnetic Aerosol Particles to Specific Regions in The Lung 51
Figs. 4.12 (a, b, c) clarify the effects of a magnetic number for position 2 with 4 𝜇𝑚
diameter particle and 60 lpm flow rates. Fig. 4.12 (a) illustrates the lung airway
deposition at the targeted position 2 for magnetic number of 0.181. The percentage of
(a) (b)
(c) (d)
Figure 4.12: Magnetic number effect (Flux value) on particle transport outline and DE
(%) for Position 2, 𝑑𝑝 = 4 𝜇𝑚, Q=60lpm,(a) 𝑀𝑛 = 0.181T;(b)𝑀𝑛 = 2.5 T; (c)𝑀𝑛 =
3 T; (d) deposition efficiency for magnetic number.
52 Chapter 4: Results and Discussion
number of deposition for magnetic number 0.181 T is 12.41. The deposited particle
for magnetic number 2.5 T is shown in Fig. 4.12 (b) and the overall deposition
percentage is 47.39. The overall deposition percentage for magnetic number 3 T is
51.63. It is estimated that increasing the magnetic number deliberately enhances the
deposition on the targeted position. Fig. 4.12(d) shows the overall deposition for
magnetic number intensity. Fig 4.12 shows that the increasing effect of the magnetic
number maximum particle goes to the target region. Therefore, the larger magnetic
number can play an important role in particulate deposition on the targeted region of
the lung.
Targeting Delivery of Magnetic Aerosol Particles to Specific Regions in The Lung 53
Figs.4.13 (a, b) represent the effect of external magnetic source in two different
positions for 4 𝜇𝑚 particle diameter, 30 lpm inhalation flow rate and 2.5 T magnetic
number. Due to the position of the magnetic source, the drug particles tend to
accelerate in the targeted position in the presence of the magnetic force. Fig.4.13 (a)
illustrates the deposition scenario for magnetic intensity in position 1 and the overall
deposition percentage is 99.33. Fig.4.13. (b) shows the respiratory deposition scenario
0
20
40
60
80
100
120
DE
(%)
Magnet position
(c)
(a) (b)
Figure 4.13: Effect of source position of magnet on particle transport outline and DE
(%) for 𝑑𝑝 = 4 𝜇𝑚, Q=30 lpm, 𝑀𝑛 = 2.5 𝑇, (a) Position 1; (b) Position 2;(c)
deposition efficiency for magnetic source position.
54 Chapter 4: Results and Discussion
for Q=30 lpm and magnetic field for position 2. The overall percentage for magnetic
source position 2 is 42.92. It is estimated that the deposition efficiency is decreased by
increasing the distance from origin along the Z axis, which is shown in Fig.4.13(c).
Therefore, in this histogram, the maximum number of deposited particles is shown in
the left lung and targeted position, which is an advantage of the current numerical
model for specific region deposition.
0
5
10
15
20
25
30
35
40
DE
(%)
Flow Rates
60 lpm
30 lpm
15 lpm
0
5
10
15
20
25
30
35
40
DE
(%)
Particle Diameter
2
4
6
(b)
0
5
10
15
20
25
30
DE
(%)
Magnetic Number
3
2.5
0.181
(c)
0
10
20
30
40
50
60
70
80
position 1 position 2
DE
(%)
Magnetic source Position
Position 1
Position 2
(d)
Figure 4.14: Local deposition efficiency for (a) flow rates; (b) Particle diameter; (c)
Magnetic number effect; (d) Magnetic source position. Generation 1 (g1), Left
Generation 2 (lg2); Right Generation 2 (rg2).
(a)
Targeting Delivery of Magnetic Aerosol Particles to Specific Regions in The Lung 55
Fig.4.14 symbolises the local DE for different flow rates, particle diameter; magnetic
number and magnetic source position. Fig.4.14 (a) represents the regional deposition
scenario for three different flow rates i.e. 15 lpm, 30 lpm and 60 lpm. The deposition
percentage in targeted position (wall position 2) for these three different flow rates are
23.84, 4.027 and 36.30 respectively. The drug particle deposition concentration in the
targeted position is higher than other region for 2 μm due to lower inertia. When the
flow rate is fast i.e. 60 lpm and the magnetic number is 2.5 T, the maximum number
of particles is deposited in wall position 2, which is the targeted position as shown in
Fig.4.14 (a). Fig.4.14 (b) shows the local deposition efficiency for three different
particle diameters i.e. 2 μm, 4 μm and 6 μm. From Fig.4.14 (b) the local deposition
percentage in targeted position for 2 μm particle diameter is 12.33, 4 μm particle
diameter is 36.30 and 6 μm particle diameter is 20.11. For 4 μm particle diameter, the
maximum number of particles is deposited in targeted position in Fig.4.14 (b). On the
other hand, the overall deposition is higher for 6 μm particle diameter than other
particle diameters due to larger inertia. Fig.4.14 (c) illustrates the local deposition
scenario for three different magnetic numbers i.e. 0.181 T, 2.5 T, 3 T and percentages
of deposition particles in targeted position (wall position 2) are 2.27, 36.30 and 4.14
respectively. Due to the large magnetic number, the overall deposition is higher for
magnetic number 3 T. Fig.4.14 (d) shows the local deposition for two different
magnetic source positions. When the magnetic field is in position 1, flow rate is
medium (30 lpm), and for particle diameter 4 μm most of the particle is deposited on
the wall position 1 and generation 1. Similarly, when the magnetic intensity is in
position 2, the maximum number of particles is deposited in left branch and wall
position 2. The deposition scenario shows higher deposition on left lung and targeted
position in Fig.4.14.
56 Chapter 4: Results and Discussion
4.2 CASE STUDY 2: MAGNETIC NANOPARTICLE
4.2.1 COMPUTATIONAL DOMAIN AND MESH GENERATION:
The 2-generation lung symmetric model is constructed to calculate the complex
flow field in a human lung. This 2- generation lung geometry contains 1.5 million
elements and 0.54 million nodes. An inflation of 10 boundary layer mesh was
constructed near the solid wall.
Figure 4.15: (a) Anterior view of the 2-generation mesh with 0.54 million unstructured
cells, (b) interior view and inflation layer mesh near to the wall, (c) inlet mesh, (d)
outlet mesh of 2-generation lung model.
(a) (b)
(c) (d)
Targeting Delivery of Magnetic Aerosol Particles to Specific Regions in The Lung 57
4.2.2 GRID INDEPENDENCE TEST:
Due to the sensitive results of regional turbulence effects, a grid resolution test
is performed for adequately refining and choosing the appropriate final mesh for this
present study. This model is tested for different grid numbers as a function of
maximum pressure, which is calculated on the outlet plane. The flow seems converged
from the red point and it is conceivable to use any of the grid cells from this point.
However, 0.54 million nodes is adopted for the present simulations.
Figure 4.16: Maximum pressure grid convergence
4.2.3 MODEL VALIDATION:
A comprehensive validation has been performed for the present study. The
present 2- generation nano-particle simulation result has been compared with various
published results of CFD.
Fig.4.17 shows the nano-particle DE compared with experimental results of a double
bifurcation model (G3-G5) of Kim (2002) . The results were validated for the first and
second bifurcation of the present 2- generation model. The current model have also
been compared with the CFD result of Zhang and Kleinstreuer (2004) for a different
0
2
4
6
8
10
12
14
16
0 100000 200000 300000 400000 500000 600000 700000 800000
Max
imum
pre
ssure
(pas
cal)
Grid Number
58 Chapter 4: Results and Discussion
inlet Reynolds number (Re = 200, 500 and 1000) and (Islam et al., 2017) for two
different inlet Reynolds number (Re = 200, 550). Fig.4.17 (a) shows comparison of
nano-particle deposition for the first bifurcation and Fig.4.17 (b) shows the deposition
comparison for the second bifurcation. The present NPs DE shows good agreement
with the published experimental data for both bifurcations.
Figure 4.17. Nano-particle DE comparison with the experimental data of Kim (2002)
and the CFD results of Zhang and Kleinstreuer (2004) and (Islam et al., 2017), in a
double bifurcation model (G3-G5), (a) first bifurcation, and (b) second bifurcation.
(a) (b)
Figure 4.18 Deposition fraction (DF) of Nano-particle comparison with the CFD
results of Zhang and Kleinstreuer (2004) across different bifurcation for 30 lpm flow
rates in the bifurcation airway model.
Targeting Delivery of Magnetic Aerosol Particles to Specific Regions in The Lung 59
Fig.4.18 shows the nano-particle DF compared with CFD results of a double
bifurcation model of Zhang and Kleinstreuer (2004). The results were validated for 30
lpm flow rate and the first and second bifurcation of the present 2- generation model.
The present result DF is about the same for both bifurcation with the published result.
The present nano-particle DF shows good agreement with the published CFD data for
both bifurcations.
The 2- generation lung model specification and external magnetic source position has
been indicated in Fig.4.19. Position 1 and Position 2 indicate the external magnetic
field source. Magnet position 1 has been set just before the first bifurcation and
position 2 has been set on the right lung, as are shown in Fig.4.19. The present model’s
left and right side are indicated by lg2 (left generation 2) and rg2 (right generation 2).
4.2.4 POST PROCESSING RESULTS FOR MAGNETIC NANOPARTICLE
The present 2-generation lung airway model has been designed to calculate the
nano-particle exact deposition in the targeted position and lung region. Fig.4.20 shows
Figure 4.19: Geometry specification of 2-generation model (Magnet position 2 has been
set on the right lung).
60 Chapter 4: Results and Discussion
the particle TD for flow rate variation along the two selected external magnetic field
positions for 1-nm particle diameter and Mn=2.5 T.
Figure 4.20: Effect of Flow Rates on particle transport outline for position 1 and
position 2, Mn=2.5 T, dp=1-nm, (a) 7.5 lpm for position 1; (b) 7.5 lpm for position 2;
(c) 9 lpm for position 1; (d) 9 lpm for position 2; (e) 15 lpm for position 1; (f) 15 lpm
for position 2; (g) Overall deposition efficiency.
(e) (f)
(g)
0
20
40
60
80
100
120
Position 1 Position 2
Dep
osi
tion
eff
icie
ncy
Position of magnet
7.5 lpm9 lpm15 lpm
(g)
(a) (b)
(d)
(c)
Targeting Delivery of Magnetic Aerosol Particles to Specific Regions in The Lung 61
Fig.4.20 represents the deposition efficiency for three different breathing flow rates
(sleeping, resting and slow) at two different magnetic field positions (position 1 and
position 2). Figs.4.20 (a, b) represent the deposition efficiency for 7.5 lpm flow rate
for position 1 and position 2 respectively. At sleeping breathing condition (7.5 lpm),
NPs deposition at the targeted position 1 and position 2 are significantly increased
more than any other region, as shown in Figs.4.20 (a, b). The total percentage of
deposition for sleeping breathing condition, at position 1 and position 2 are 96.24 and
41.14. At 9 lpm, which represents the resting breathing condition, the total deposition
percentage for position 1 and position 2 are 56.67 and 39.33, shown in Figs.4.20 (c,
d). The total percentages of deposition during slow breathing condition (15 lpm), at
position 1 and position 2, are 22.60 and 20.24, shown in Figs.4.20 (e, f). From the
deposition scenario of 1-nm diameter particle is found that under the sleeping
condition, a higher number of 1-nm particles are deposited in position 1 and position
2 than under other breathing conditions. Fig.4.20 (g) shows the overall deposition
efficiency for three different flow rates. The overall deposition pattern shows that the
Brownian motion is effective for smaller flow rates. The effect of Brownian motion is
that it increases with the decrease of flow rates. The overall deposition pattern for
different flow rates of 1-nm diameter particles satisfies the general assumption of
Brownian motion and shows that depending on the lower flow rates, this Brownian
motion is dominant in the upper airways. The DE scenario of MNPs, decreases with
the increasing of flow rates because of low residence time.
62 Chapter 4: Results and Discussion
Figure 4.21: Effect of magnetic number on particle transport outline for Position 1 and
position 2, 7.5 lpm, dp=1-nm, (a) Mn=0.181 T for position 1; (b) Mn=0.181T for
position 2 ; (c) Mn=1.5 T for position 1; (d) Mn=1.5 T for position 2; (e) Mn=2.5 T
for position 1; (f) Mn=2.5 T for position 2; (g) Overall deposition efficiency for
magnetic position 1 and magnetic position 2.
(e) (f)
0
20
40
60
80
100
120
Position 1 Position 2
Dep
osi
tion
eff
icie
ncy
(%)
position of magnet
Mn=0.181
Mn=1.5
Mn=2.5
(g)
(a) (b) (c)
(d)
Targeting Delivery of Magnetic Aerosol Particles to Specific Regions in The Lung 63
Fig.4.21 clarifies the effects of magnetic number (magnetic intensity) at position 1 and
position 2 with 1 -nm particle and 7.5 lpm flow rates. Figs.4.21 (a, b) shows the lung
airways’ deposition scenario for magnetic number 0.181 T at the targeted position 1
and position 2. The number of total deposition percentages for magnetic number 0.181
T, at the targeted position 1 and position 2, are 74.01 and 32.41. The deposited particles
for magnetic number 1.5 T are shown in Figs.4.21 (c, d). The overall percentages for
magnetic number 1.5 T at the targeted position 1 and position 2 are 74.05 and 40.72.
Figs. 4.21 (e, f) show the Particle TD at targeted position 1 and position 2 for magnetic
number 2.5. The overall deposition percentages for magnetic number 2.5 T, at the
targeted position 1 and position 2, are 96.24 and 41.14. It is estimated that increasing
the magnetic number deliberately enhances the deposition on the targeted position.
From the deposition scenario of 1-nm diameter particle is found that, under the effect
of magnetic number 2.5 and flow rate 7.5 lpm, a higher number of 1-nm particles are
deposited in position 1 and position 2 than for other magnetic numbers. Fig.4.21 (g)
shows the overall deposition efficiency at the targeted position 1 and position 2 for
three different magnetic numbers. Therefore, the larger magnetic number can play an
important role in particulate deposition on the targeted region of the lung. The overall
deposition pattern for 1-nm diameter particle effect of a magnetic number satisfies the
general assumption of magnetic intensity. The DE of MNPs is estimated to enhance
with the increase of the magnetic number (Oveis Pourmehran et al., 2016). According
to the above MNPs’ deposition scenario, the deposition value at the targeted region
(right lung) is substantially greater than at the other region of lung (left lung). So, the
targeting magnetic drug delivery technique satisfies the advantage of the current
targeted drug delivery system.
64 Chapter 4: Results and Discussion
Figure 4.22: Particle Traces Coloured by Turbulent Kinetic Energy (k) (𝑚2/𝑆2) for 60
lpm, Mn=2.5 T and magnet position 2, (a) 1- nm; (b) 10- nm; (c) 50- nm; (d) 100- nm;
(e) 500- nm.
(a) (b)
(c) (d)
Turbulent kinetic Energy
(e)
Targeting Delivery of Magnetic Aerosol Particles to Specific Regions in The Lung 65
Fig.4.22 shows the particle tracing coloured by Turbulent Kinetic Energy (TKE) at
magnet position 2, 60 lpm flow rates and Mn=2.5 T for different particle diameters.
The path of a particle is a unique path for a particle injected at a given location (inlet)
in the flow. Particle trajectories are not deterministic and two identical particles,
injected from a single point at different times, may follow separate trajectories due to
the random nature of the instantaneous fluid velocity. It is the fluctuating component
of the fluid velocity that causes the dispersion of particles in a turbulent flow. In
turbulent flow, the speed of the fluid at a point is continuously undergoing changes in
both magnitude and direction. The intensity of turbulence is measured by TKE. TKE
provides the reduction of turbulence with time. This causes the energy to be dissipated
from large vortices to small ones. It is recognised that for TKE, airflow rapidly goes
faster in the compression region and as a result, the maximum number of particles is
deposited on that region. The turbulent kinetic energy is calculated as:
𝑘 =3
2[𝐼𝑑𝑒𝑓max (𝑈𝑠, |𝑈𝐼𝐺|, 𝑈𝜔)]2
(4.1)
𝐼𝑑𝑒𝑓 is the default turbulent intensity, 𝑈𝑠 is a minimum velocity, 𝑈𝐼𝐺 is the velocity
initial guess and 𝑈𝜔 is the product of the simulation average length scale and the
rotation rate.
66 Chapter 4: Results and Discussion
Figure 4.23: Particle Traces Coloured by particle residence time at magnetic position
2 for 60 lpm and Mn=2.5 T (a) 1- nm; (b) 10- nm; (c) 50- nm; (d) 100- nm; (e) 500-
nm.
Particle residence time
(a) (b)
(c) (d)
(e)
Targeting Delivery of Magnetic Aerosol Particles to Specific Regions in The Lung 67
Fig.4.23 shows the particle tracing coloured by particle residence time at magnet
position 2, 60 lpm flow rates and Mn=2.5 T for different particle diameters. Figs.4.23
(a, b, c, d, and e) show the particle residence time for 1-nm, 10-nm, 50-nm, 100-nm,
and 500-nm particle diameter. Residence time is the average amount of time spent in
a control volume by the particles of a fluid. For the medical field, the amount of time
that a drug spends in the body is usually referred to by residence time. This is
dependent on the amount of the drug and an individual’s body size. The residence
time is different for each and every drug based on its chemical composition and
technique of administration. Some of the drug molecules stay in this system for a very
short time, while others may remain for a lifetime. To find a mean residence time,
groups of aerosolised drug particles are tracked and plotted due to hard tracing of
residence time for individual particles. Comparing the drug particle residence time in
the present study, Fig.4.23 (e) shows that 500-nm MNPs diameter spend more time
inside the lung than other particle MNPs diameter residence time.
68 Chapter 4: Results and Discussion
Figure 4.24: Deposition Efficiency comparisons for nano particles of various diameter
and flow rates at position 1 and position 2 for magnetic number 2.5 T.
Table 4.1. Respiratory particle TD comparisons for 1-, 50-, 100- and 500-nm diameter
particles as a function of different breathing airflow rates and magnetic number
2.5T.Posi 1(position 1), Posi 2 (position 2).
7.5 lpm 9 lpm 15 lpm 60 lpm
Diameter Posi 1 Posi 2 Posi 1 Posi 2 Posi 1 Posi 2 Posi 1 Posi 2
1-nm 96.24% 41.14%
56.67%
39.33%
22.60%
20.24%
63.97%
39.90%
50- nm 26.20%
13.87%
30.77%
26.82%
70.72%
18.20%
86.91%
41.59%
100- nm 30.79%
11.45%
21.80% 7.70%
44.40%
13.54%
62.81%
52.71%
500- nm 30.83%
10.93%
47.49%
44.80%
84.52%
23.50%
78.35%
70.83%
0
20
40
60
80
100
120
position 1 position 2 position 1 position 2 position 1 position 2 position 1 position 2
1 nm 50 nm 100 nm 500 nm
Dep
osi
tio
n e
ffic
ien
cy
Diameter and Magnet position
7.5 lpm
9 lpm
15 lpm
60 lpm
Targeting Delivery of Magnetic Aerosol Particles to Specific Regions in The Lung 69
The NPs DE comparison in two different magnetic field positions of the 2-generation
symmetric lung model at different flow rates and diameter are shown in Fig.4.24. The
DE at two different magnetic field positions is different for particle diameter and flow
rates. Overall DE comparison shows higher deposition concentration in the magnetic
field position 1 than position 2. Fig.4.24 clearly shows the distinct deposition for
different diameter particles at different flow rates for magnetic number 2.5 T. Fig.4.24
also shows the maximum number of particles deposited in position 1 is 96.24% for
flow rate 7.5 lpm and 1-nm particle diameter. On the other hand, at the targeted
position 2, the number of deposition percentage is at maximum (70.83%) for flow rate
60 lpm and particle diameter 500-nm. The deposition efficiency trend line for flow
rates 7.5 lpm shows that when the magnetic source is in position 1, the maximum
number of particles is deposited for 1-nm diameter than for other particle sizes.
Table 4.1 shows the total flow rate and diameter TD percentage comparison across
two different magnetic field positions for magnetic number 2.5 T. Table 4.1 also shows
that the total flow of deposition concentration is higher in magnetic field position 1
than in position 2.
70 Chapter 4: Results and Discussion
Figure 4.25: Deposition Efficiency comparisons for nano particles of various
diameters and magnetic number at position 1 and position 2 for 15 lpm flow rates.
Table 4.2. Respiratory particle TD comparisons at two different targeted positions for
0.181 T, 1.5 T, and 2.5 T magnetic number as a function of 15lpm breathing
airflow rates and 1-, 50-, 100- and 500-nm diameter particle.
Mn=0.181 T Mn=1.5 T Mn=2.5 T
Diameter Position
1
Position
2
Position 1 Position
2
Position 1 Position 2
1 nm 95.27% 52.82% 51.11% 25.08% 22.60% 20.24%
10 nm 90.22% 15.04% 64.45% 13.62% 27.46% 15.04%
50 nm 92.49% 27.25% 49.13% 14.38% 70.72% 18.20%
100 nm 99.40% 17.14% 77.09% 15.42% 44.40% 13.54%
500 nm 91.64% 0.019% 97.72% 23.27% 84.52% 23.50%
0
20
40
60
80
100
120
position 1 position 2 position 1 position 2 position 1 position 2
mn=0.18 mn=1.5 mn=2.5
Dep
osi
tio
n E
ffic
ien
cy
Magnet Position
1 nm
10 nm
50 nm
100 nm
500 nm
Targeting Delivery of Magnetic Aerosol Particles to Specific Regions in The Lung 71
Fig.4.25 clarifies the effects of magnetic number for targeted drug delivery at magnetic
position 1 and position 2 with 15 lpm flow rates and 1-nm, 50-nm, 100-nm and 500-
nm diameter particles. The overall deposition is significantly higher for small magnetic
number 0.181 T than other magnetic numbers. The DE trend line for 1-nm particle
diameter for 15 lpm breathing condition shows a linear trend line for position 1 and
position 2. The deposition trend line of 1-nm, 10-nm and 100-nm particle is
significantly increased in small magnetic numbers for both magnetic field positions,
then decreases as magnetic number increases, shown in Fig.4.25. The deposition trend
lines for 50-nm and 500-nm are fluctuating during the changes of magnetic number.
Due to the position of magnetic source, the MNPs tend to accelerate along the targeted
position in the presence of magnetic intensity. These specific findings can play an
important role in targeted drug delivery.
Table 4.2. Shows the overall particle TD comparisons at two different targeted
positions and different particle diameters for 0.181 T, 1.5 T, and 2.5 T magnetic
numbers as a function of 15 lpm slow breathing airflow rates. Therefore, the smaller
magnetic number can play an important role in particulate deposition on the targeted
region of lung during slow breathing condition.
72 Chapter 4: Results and Discussion
Figure 4.26: Regional particle deposition efficiency in each zone at different particle
sizes, magnet position, magnetic number 2.5 T and inhalation rates. Generation 1 (g1),
Left Generation 2 (lg2), Right Generation 2 (rg2).
In order to classify the regional deposition of targeted delivery of NPs, the airway
geometry is specified in three regions according to Fig.4.26 and local deposition
efficiency in each zone at various inhalation flow rates, particle sizes, and magnetic
field position are calculated and shown in Fig.4.26. Figs.4.26 (a, b, c, d) symbolise the
local deposition efficiency for 7.5 lpm, 9lpm, 15 lpm and 60 lpm flow rates and
magnetic number 2.5. Due to external magnetic field being set on the right lung and
0
10
20
30
40
50
60
posi
tion
1
posi
tion
2
posi
tion
1
posi
tion
2
posi
tion
1
posi
tion
2
posi
tion
1
posi
tion
2
posi
tion
1
posi
tion
2
1-nm 10-nm 50-nm 100-
nm
500-
nm
Dep
osi
tio
n E
ffic
ien
cy
Diameter and Magnet position
g1
rg2
wall position 1
lg2
Flow Rate 9 lpm and Mn 2.5
(b)
0
10
20
30
40
50
60
70
80
posi
tion
1
posi
tion
2
posi
tion
1
posi
tion
2
posi
tion
1
posi
tion
2
posi
tion
1
posi
tion
2
posi
tion
1
posi
tion
2
1- nm 10- nm 50- nm 100- nm 500- nm
Dep
osi
tion E
ffic
iency
Diameter and Magnet Position
g1
rg2
wall position 1
lg2
Flow Rate 15 lpm and Mn 2.5
0
10
20
30
40
50
60
70
80
90
posi
tion
1
posi
tion
2
posi
tion
1
posi
tion
2
posi
tion
1
posi
tion
2
posi
tion
1
posi
tion
2
posi
tion
1
posi
tion
21- nm 10- nm 50- nm 100- nm500- nm
Dep
osi
tion E
ffic
iency
Diameter and Magnet Position
g1rg2wall position 1lg2
Flow Rate 60 lpm and Mn 2.5
(d)
0
10
20
30
40
50
60
70
80
90
100
posi
tion
1
posi
tion
2
posi
tion
1
posi
tion
2
posi
tion
1
posi
tion
2
posi
tion
1
posi
tion
2
posi
tion
1
posi
tion
2
1- nm 10-nm 50-nm 100-nm 500-nm
Dep
osi
tio
n E
ffic
ien
cy
Diameter and Magnet Position
g1
rg2
wall position 1
lg2
Flow Rate 7.5 lpm and Mn 2.5
(a)
(c)
Targeting Delivery of Magnetic Aerosol Particles to Specific Regions in The Lung 73
before the first bifurcation, the deposition percentage is significantly increased in
generation 1 of the right lung (rg2). For sleeping (7.5 lpm) and resting (9 lpm)
conditions, the regional deposition concentration is higher in generation 1 of 1-nm
particle diameters than other regions in Fig.4.26 (a, b). Fig.4.26 (c) shows the region
deposition efficiency at two different magnetic positions for slow breathing condition
(15 lpm) and magnetic number 2.5 T. This figure shows that maximum regional
deposition is held in generation 1 for 500-nm. Fig.4.26 (d) shows the overall regional
deposition for fast breathing condition (60 lpm) and magnetic number 2.5T. During
the fast breathing pattern, the maximum number of regional depositions is calculated
in generation 1 for 50-nm particles. The present 2-generation symmetrical airway
model allows comprehensive NPs deposition data at different regions, which could
potentially increase an understanding of targeted region deposition and specifically,
the transport of magnetic nanoparticles to the targeted drug delivery system.
74 Chapter 5: Conclusion
Chapter 5 : CONCLUSIONS
5.1 CONCLUSIONS
In this thesis, 2-generation lung models were developed. An advance meshing
technique was used to predict the more accurate magnetic drug particle TD in the
specific region of the human lung. Pharmaceutical aerosol particle TD has been
investigated for different magnetic field positions, magnetic numbers, particle
diameters and various breathing conditions.
Magnetic aerosol particle transport and deposition has been investigated for the
targeted region of the lung for two different magnetic field positions. A symmetrical
model of the lung is constructed from the geometry generation software of solid works
and ANSYS 18. Two different magnetic field positions are developed for investigating
the targeting of drug delivery of magnetic aerosol particles. A new deposition
technique is observed for the present lung model, which could minimise the unwanted
side effects and improve the overall DE of the targeted drug delivery to the specific
region of lung airways. The study also depicts that magnetic field, magnetic number
and inhalation flow rates greatly influence the magnetic aerosol particle deposition in
the targeted region of the lung.
Magnetic microparticle TD in the specific position of a 2-generation symmetric
bronchial tree model by external magnetic field has been performed for the first time.
The advanced numerical model illustrates the magnetic aerosol particle TD
phenomena in the specific region of lung airways. Detailed deposition patterns at two
different magnetic field positions are performed for different magnetic numbers,
breathing conditions and a wide range of monodisperse particles. Numerical results
Targeting Delivery of Magnetic Aerosol Particles to Specific Regions in The Lung 75
illustrate that magnetic aerosol particle DE in the left lung (targeted region) is higher
than the right lung. A different deposition mechanism is observed and the findings of
this study will help the pharmaceutical industry to design new drug delivery devices.
The study will increase the efficiency of the targeted drug delivery to the specific
region of a lung model.
A comprehensive MNPs TD analysis has been performed in the targeted region
of a 2-generation lung model. Sleeping, resting, slow breathing condition and fast
breathing physical conditions are considered, to predict the magnetic targeting of drug
delivery in the specific region of the lung. MNPs deposition efficiency in the specific
region of 3-generation lung have been performed and a non-linear trend is observed,
which could increase the understanding of the health risk assessment of lung diseases.
A significant deposition efficiency is observed in two different specific positions of
the lung for various magnetic numbers, physical conditions and particle diameters, and
this could potentially help the development of future therapeutics. The findings of the
present study would improve the knowledge of magnetic targeting drug delivery and
could potentially help in the specific region of drug delivery.
To sum up, the advanced numerical model and the findings of the present study
will advance the pharmaceutical drug delivery system. The present findings will help
to design drug delivery systems for the pharmaceutical companies to deliver drugs to
specific regions of the lung. These particular findings may be used to develop a more
realistic drug delivery system in a targeted position of the human lung.
76 Chapter 5: Conclusion
5.2 LIMITATIONS AND FUTURE STUDY
The present advanced CFD approach still has some limitations. Some specific
limitations and future recommendations are listed below:
i) The present model used 2-generation geometry. A realistic model, more
generations and a patient-specific sample model need to be used for
better prediction of magnetic particle TD in the specific region of the
human lung.
ii) The present model considers only steady state and does not consider the
transient state. The transient case may increase the understanding of
particle deposition in the specific region of the human lung.
iii) Only monodisperse magnetic particles are considered in this study.
Polydisperse particles could be considered for better prediction.
iv) This study only considers one-way inhalation to predict the magnetic
particle TD in the lung airways. The two-way inhalation and exhalation
effects might aid in the understanding of particle TD.
v) The present magnetic particle TD study did not consider any breath-
holding effects on deposition in the targeted position for different flow
rates.
Targeting Delivery of Magnetic Aerosol Particles to Specific Regions in The Lung 77
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Targeting Delivery of Magnetic Aerosol Particles to Specific Regions in The Lung 83
APPENDICES
In the main chapter 4, the result of magnetic micro particle and magnetic nano
particle have been presented and this appendices chapter shows some sensitive result
for case study 1 (magnetic micro particle) and case study 2 (magnetic nano particle).
A: CASE STUDY 1 (MAGNETIC MICRO PARTICLE)
A1: MESH GENERATION
Figure A.1: (a) interior view of the 2-generation mesh.
This 2-generation lung geometry contains 450,429 elements and 179,660 nodes. A
proper grid refinement test has been conducted and the final geometry contains
179,660 nodes for magnetic micro particle simulations.
84 Appendices
A2: FLOW RATES EFFECT
Figs. A. 2: (a, b, c) represent the deposition efficiency for three different breathing
flow rates (slow, medium and fast) i.e., 15 lpm, 30 lpm and 60 lpm respectively when
the magnetic number, 𝑀𝑛 = 0.25 T, magnetic source position is in position 2 and the
particle diameter is 4 𝜇𝑚.
(a) (b)
(c) (d)
Figure A.2: Effect of flow rates on particle transport outline and DE (%) for Position
2, 𝑑𝑝 = 4 𝜇𝑚, 𝑀𝑛 = 0.25 𝑇 , (a) 15 lpm; (b) 30 lpm; (c) 60 lpm; (d) Total deposition
efficiency in terms of flow rates.
Targeting Delivery of Magnetic Aerosol Particles to Specific Regions in The Lung 85
A3: PARTICLE DIAMETER EFFECT
Figs. A. 3: (a, b, c) represent the deposition efficiency for three different micro particle
diameter i.e., 2 μm, 4 μm and 6 μm respectively when the magnetic number, 𝑀𝑛 =
0.25 T, magnetic source position is in position 2 and the flow rates is 60 lpm.
(a) (b)
(d)
(c)
Figure A.3: Effect of particle diameter on particle transport outline and DE (%) for
Position 2, 𝑀𝑛 = 0.25 𝑇, Q=60 lpm (a) 𝑑𝑝 = 2 𝜇𝑚; (b) 𝑑𝑝 = 4 𝜇𝑚; (c) 𝑑𝑝 = 6 𝜇𝑚;
(d) deposition efficiency.
86 Appendices
A4: MAGNETIC FIELD (POSITION) EFFECT
Figure A.4: Effect of magnetic field on particle TD outline for (a) position 1; (b)
particle traces by particle id for magnet position 2.
Position 1
Position 2
(a) (b)
Figure A.5: Magnitude of �� (magnetic flux density) vector for position 2.
Targeting Delivery of Magnetic Aerosol Particles to Specific Regions in The Lung 87
B: CASE STUDY 2 (MAGNETIC NANO PARTICLE)
B1: EFFECT OF FLOW RATES ON PARTICLE TD FOR MAGNETIC FIELD
POSITION1, MN=2.5 AND DIFFERENT PARTICLE DIAMETER
Figure A.6: Effect of flow rates on particle transport outline for particle diameter 1-nm,
10- nm, 50-nm,100-nm,500-nm, position 1, Mn=2.5T, (a) 1-nm for 7.5 lpm; (b) 10-nm
for 7.5 lpm; (c) 50-nm for 7.5 lpm; (d) 100-nm for 7.5 lpm; (e) 500-nm for 7.5 lpm; (f)
1-nm for 9 lpm; (g) 10-nm for 9 lpm; (h) 50-nm for 9 lpm; (i) 100-nm for 9 lpm; (j)
500-nm for 9 lpm; (k) 1-nm for 15 lpm; (l) 10-nm for 15 lpm; (m) 50-nm for 15 lpm;
(n) 100-nm for 15 lpm; (o) 500-nm for 15 lpm; (p) 1-nm for 60 lpm; (q) 10-nm for 60
lpm; (r) 50-nm for 60 lpm; (s) 100-nm for 60 lpm; (t) 500-nm for 60 lpm.
88 Appendices
B2: EFFECT OF FLOW RATES ON PARTICLE TD FOR MAGNETIC FIELD
POSITION 2, MN=2.5 AND DIFFERENT PARTICLE DIAMETE
Figure A.7: Effect of flow rates on particle transport outline for particle diameter 1-nm, 10-
nm, 50-nm,100-nm,500-nm, position 2, Mn=2.5T, (a) 1-nm for 7.5 lpm; (b) 10-nm for 7.5
lpm; (c) 50-nm for 7.5 lpm; (d) 100-nm for 7.5 lpm; (e) 500-nm for 7.5 lpm; (f) 1-nm for 9
lpm; (g) 10-nm for 9 lpm; (h) 50-nm for 9 lpm; (i) 100-nm for 9 lpm; (j) 500-nm for 9 lpm;
(k) 1-nm for 15 lpm; (l) 10-nm for 15 lpm; (m) 50-nm for 15 lpm; (n) 100-nm for 15 lpm;
(o) 500-nm for 15 lpm; (p) 1-nm for 60 lpm; (q) 10-nm for 60 lpm; (r) 50-nm for 60 lpm;
(s) 100-nm for 60 lpm; (t) 500-nm for 60 lpm.
Targeting Delivery of Magnetic Aerosol Particles to Specific Regions in The Lung 89
B3: PARTICLE DIAMETER AND MAGNETIC POSITION EFFECT FOR
MN=0.18 AND 15 LPM FLOW RATES
Figure A.8: Effect of particle diameter and magnet position on particle transport outline
Mn= 0.18T, flow rates 15 lpm, (a) 1-nm for position 1; (b) 1-nm for position 2; (c) 10-
nm for position 1; (d) 10-nm for position 2; (e) 50-nm for position 1; (f) 50-nm for
position 2.
(a) (b) (c)
(d) (e) (f)
90 Appendices
B4: DEPOSITION EFFICIENCY HISTOGRAM FOR MAGNETIC FIELD
POSITION 1
Figure A.9: Deposition Efficiency comparisons for NPs of various diameter and flow
rates at position 1 for magnetic number 2.5T.
B5: DEPOSITION EFFICIENCY HISTOGRAM FOR MAGNETIC FIELD
POSITION 2
Figure A.10: Deposition Efficiency comparisons for NPs of various diameter and
flow rates at position 2 for magnetic number 2.5T.
0
10
20
30
40
50
60
70
80
1 nm 10 nm 50 nm 100 nm 500 nm
Dep
osi
tio
n E
ffic
ien
cy(%
)
particle Diameter
7.5 lpm
9 lpm
15 lpm
60 lpm
0
20
40
60
80
100
120
1 nm 10 nm 50 nm 100 nm 500 nm
Dep
osi
tion
Eff
icie
ncy
(%)
Particle Diameter
7.5 lpm
9 lpm
15 lpm
60 lpm
Targeting Delivery of Magnetic Aerosol Particles to Specific Regions in The Lung 91
B6: REGIONAL DEPOSITION EFFICIENCY FOR 15 LPM AND MN 0.181
Figure A.11: Regional particle deposition efficiency in each zone at different
particle sizes, magnet position, magnetic number 0.181T and 15 lpm flow rates.
0
20
40
60
80
100
120
posi
tion 1
posi
tion 2
posi
tion 1
posi
tion 2
posi
tion 1
posi
tion 2
po
siti
on 1
posi
tion 2
posi
tion 1
po
siti
on 2
1-nm 10-nm 50-nm 100-nm 500-nm
Dep
osi
tion E
ffic
iency
Diameter and Magnet Position
g1
rg2
wall position 1
lg2
Flow Rate 15 lpm and Mn 0.181 T
92 Appendices
B7: REGIONAL DEPOSITION EFFICIENCY FOR 15 LPM AND MN 1.5
Figure A.12: Regional particle deposition efficiency in each zone at different
particle sizes, magnet position, magnetic number 1.5 T and 15 lpm flow rates.
B8: STATIC PRESSURE FOR POSITION 2
0
10
20
30
40
50
60
70
80
90
100
position
1
position
2
position
1
position
2
position
1
position
2
position
1
position
2
position
1
position
2
1-nm 10-nm 50-nm 100- nm 500-nm
Dep
osi
tion E
ffic
iency
Diameter and Magnet Position
g1
rg2
wall position 1
lg2
Flow Rate 15 lpm and Mn
Static pressure
Figure A.13: Static pressure for position 2, Mn=2.5 T, 1-nm, 9 lpm