Abstract
Administration of drug in the form of particles through inhalation is generally preferable in the treatment of respiratory disorders. Conventional inhalation therapy devices such as inhalers and nebulizers, nevertheless, suffer from low delivery efficiencies, wherein only a small fraction of the inhaled drug reaches the lower respiratory tract. This is primarily because these devices are not able to produce a sufficiently fine drug mist that has aerodynamic diameters on the order of a few microns. This study employs computational fluid dynamics to investigate the transport and deposition of the drug particles produced by a new aerosolization technique driven by surface acoustic waves (SAWs) into an in silico lung model geometrically reconstructed using computed tomography scanning. The particles generated by the SAW are released in different locations in a spacer chamber attached to a lung model extending from the mouth to the 6th generation of the lung bronchial tree. An Eulerian approach is used to solve the Navier–Stokes equations that govern the airflow within the respiratory tract, and a Lagrangian approach is adopted to track the particles, which are assumed to be spherical and inert. Due to the complexity of the lung geometry, the airflow patterns vary as it penetrates deeper into the lung. High inertia particles tend to deposit at locations where the geometry experiences a significant reduction in cross section. Our findings, nevertheless, show that the injection location can influence the delivery efficiency: Injection points close to the spacer centerline result in deeper penetration into the lung. Additionally, we found that the ratio of drug particles entering the right lung is significantly higher than the left lung, independent of the injection location. This is in good agreement with this fact that the most of airflow enters to the right lobes.
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Abbreviations
- x :
-
x-Coordinate
- y :
-
y-Coordinate
- z :
-
z-Coordinate
- \(u_i \) :
-
Mean velocity in tensor notation (m/s)
- \(u_\mathrm{f} \) :
-
Fluid (air) velocity (m/s)
- \(u_\mathrm{p} \) :
-
Particle velocity (m/s)
- \(Re_\mathrm{p} \) :
-
Particle Reynolds number (−)
- \(\vec {F}\) :
-
Total force on magnetic drug career (N)
- \(\vec {F}_\mathrm{D} \) :
-
Drag force (N)
- \(\vec {F}_\mathrm{b} \) :
-
Buoyancy force (N)
- \(\vec {F}_\mathrm{g} \) :
-
Gravitational force (N)
- \(\vec {F}_{{\text {Saffman}}} \) :
-
Saffman’s lift force (N)
- \(\vec {F}_{{\text {virtualmass}}} \) :
-
Virtual mass force (N)
- \(\vec {F}_{{\text {p. gradient}}} \) :
-
Pressure gradient force (N)
- \(\vec {F}_{{\text {Faxen}}} \) :
-
Faxen force (N)
- \(\vec {F}_{{\text {Basset}}}\) :
-
Basset force (N)
- \(\vec {F}_\mathrm{B} \) :
-
Brownian force (N)
- \(\vec {F}_\mathrm{B} \) :
-
Brownian force (N)
- \(\vec {F}_\mathrm{T} \) :
-
Thermophoretic force (N)
- \(\vec {F}_\mathrm{m} \) :
-
Magnus lift force (N)
- \(\vec {F}_\mathrm{M} \) :
-
Magnetic forces (N)
- \(V_\mathrm{p} \) :
-
Particle volume \((\hbox {m}^{3})\)
- \(d_\mathrm{p}\) :
-
Particle diameter (m)
- \(m_\mathrm{p} \) :
-
Particle mass (Kg)
- f :
-
Drag coefficient \(\left( f=a_1 +\frac{a_2 }{Re_\mathrm{p}}+\frac{a_3 }{Re_\mathrm{p}^2 }\right) \)
- t :
-
Time (s)
- \(y^{+}\) :
-
Dimensionless cell height \(\left( y^{+}=\frac{y}{v_\mathrm{f} }\sqrt{\frac{\tau _\mathrm{wall} }{\rho _\mathrm{f} }}\right) \)
- \(R_{k}, R_\omega , R_\beta \) :
-
Model constant of \(k-\omega \) LRN (−)
- \(a^{*},\alpha _\infty ^*,\alpha _0 \) :
-
Model coefficient, \(k-\omega \) LRN (−)
- \(S_{ij} \) :
-
Mean rate strain tensor \((\hbox {S}^{-1})\)
- k :
-
Turbulent kinetic energy (−)
- DE:
-
Deposition efficiency (−)
- P :
-
Mean static pressure (Pa)
- \(v_\mathrm{f} \) :
-
Kinetic molecular viscosity (\({\mu _\mathrm{f} }/\rho )\)
- \(v_\mathrm{T} \) :
-
Kinetic eddy viscosity (\({\mu _\mathrm{T} }/\rho )\)
- \(\mu _\mathrm{f} \) :
-
Kinetic viscosity \((\hbox {kg m}^{-1 }\hbox {s}^{-1})\)
- \(a_1, \alpha _2, \alpha _3 \) :
-
Model constants of the Morsi and Alexander drag law (−)
- \(\rho _\mathrm{f}\) :
-
Fluid density \((\hbox {kg m}^{-3})\)
- \(\rho _\mathrm{p} \) :
-
Particle density \((\hbox {kg m}^{-3})\)
- \(\omega \) :
-
Specific dissipation rate \((\hbox {s}^{-1})\)
- \(\beta , \beta ^{*},\beta _0, \beta _0^*\) :
-
Model constant of \(k-\omega \) LRN (−)
- \(\varOmega _{ij} \) :
-
Rate rotation tensor \((\hbox {s}^{-1})\)
- \(\tau _{ij} \) :
-
Reynolds stress tensor \((\hbox {kg m}^{-1 }\hbox {s}^{-2})\)
- \(\gamma \) :
-
Model constant of \(k-\omega \) LRN (−)
- \(\sigma _k, \sigma _d, \sigma _\omega \) :
-
Model constant of \(k-\omega \) LRN (−)
References
Agertoft L, Pedersen S, Nikandr K (1999) Drug delivery from the Turbuhaler and Nebuhaler pressurized metered dose inhaler to various age groups of children with asthma. J Aerosol Med 12:161–169
Alhasan L, Qi A, Rezk AR, Yeo LY, Chan PP (2016) Assessment of the potential of a high frequency acoustomicrofluidic nebulisation platform for inhaled stem cell therapy. Integr Biol 8:12–20
Alvarez M, Friend J, Yeo LY (2008) Rapid generation of protein aerosols and nanoparticles via surface acoustic wave atomization. Nanotechnology 19:455103
Barnes PJ (2001) New treatments for chronic obstructive pulmonary disease. Curr Opin Pharmacol 1:217–222
Bennett WD (1991) Targeting respiratory drug delivery with aerosol boluses. J Aerosol Med 4:69–78
Bennett WD, Scheuch G, Zeman KL, Brown JS, Kim C, Heyder J, Stahlhofen W (1998) Bronchial airway deposition and retention of particles in inhaled boluses: effect of anatomic dead space. J Appl Physiol 85:685–694
Bennett WD, Scheuch G, Zeman KL, Brown JS, Kim C, Heyder J, Stahlhofen W (1999) Regional deposition and retention of particles in shallow, inhaled boluses: effect of lung volume. J Appl Physiol 86:168–173
Broeders ME, Sanchis J, Levy ML, Crompton GK, Dekhuijzen PN, Group AW (2009) The ADMIT series-issues in inhalation therapy. 2. Improving technique and clinical effectiveness. Prim Care Respir J 18:76–82. doi:10.4104/pcrj.2009.00025
Carroll N, Cooke C, James A (1997) The distribution of eosinophils and lymphocytes in the large and small airways of asthmatics. Eur Respir J 10:292–300
Cheng Y-S, Zhou Y, Chen BT (1999) Particle deposition in a cast of human oral airways. Aerosol Sci Technol 31:286–300. doi:10.1080/027868299304165
Chrystyn H, Price D (2009) Not all asthma inhalers are the same: factors to consider when prescribing an inhaler. Prim Care Respir J 18:243–249. doi:10.4104/pcrj.2009.00029
Cloupeau M, Prunet-Foch B (1994) Electrohydrodynamic spraying functioning modes: a critical review. J Aerosol Sci 25:1021–1036
Cochrane MG, Bala MV, Downs KE, Mauskopf J, Ben-Joseph RH (2000) Inhaled corticosteroids for asthma therapy: patient compliance, devices, and inhalation technique. Chest 117:542–550
Collins DJ, Manor O, Winkler A, Schmidt H, Friend JR, Yeo LY (2012) Atomization off thin water films generated by high-frequency substrate wave vibrations. Phys Rev E 86:056312
Cortez-Jugo C, Qi A, Rajapaksa A, Friend JR, Yeo LY (2015) Pulmonary monoclonal antibody delivery via a portable microfluidic nebulization platform. Biomicrofluidics 9:052603
Crowe CT, Schwarzkopf JD, Sommerfeld M, Tsuji Y (2011) Multiphase flows with droplets and particles. CRC Press, Boca Raton
Cui XG, Gutheil E (2011) Large eddy simulation of the unsteady flow-field in an idealized human mouth-throat configuration. J Biomech 44:2768–2774
Dalby R, Suman J (2003) Inhalation therapy: technological milestones in asthma treatment. Adv Drug Deliv Rev 55:779–791
Darquenne C (2012) Aerosol deposition in health and disease. J Aerosol Med Pulm Drug Deliv 25:140–147. doi:10.1089/jamp.2011.0916
Elcner J, Lizal F, Jedelsky J, Jicha M, Chovancova M (2016) Numerical investigation of inspiratory airflow in a realistic model of the human tracheobronchial airways and a comparison with experimental results. Biomech Model Mechanobiol 15:447–469
Fresconi FE, Prasad AK (2007) Secondary velocity fields in the conducting airways of the human lung. J Biomech Eng 129:722–732
Frijlink H, De Boer A (2004) Dry powder inhalers for pulmonary drug delivery. Expert Opin Drug Deliv 1:67–86
Grace J, Marijnissen J (1994) A review of liquid atomization by electrical means. J Aerosol Sci 25:1005–1019
Han R, Papadopoulos G, Greenspan BJ (2002) Flow field measurement inside the mouthpiece of the spiros inhaler using particle image velocimetry. Aerosol Sci Technol 36:329–341. doi:10.1080/027868202753504524
Haughney J, Price D, Barnes NC, Virchow JC, Roche N, Chrystyn H (2010) Choosing inhaler devices for people with asthma: current knowledge and outstanding research needs. Respir Med 104:1237–1245. doi:10.1016/j.rmed.2010.04.012
Hickey AJ (ed) (2003) Pharmaceutical inhalation aerosol technology, 2nd edn. CRC Press, Hoboken
Horsfield K, Dart G, Olson DE, Filley GF, Cumming G (1971) Models of the human bronchial tree. J Appl Physiol 31:207–217
Jin H, Fan J, Zeng M, Cen K (2007) Large eddy simulation of inhaled particle deposition within the human upper respiratory tract. J Aerosol Sci 38:257–268
Ju J, Yamagata Y, Ohmori H, Higuchi T (2008) High-frequency surface acoustic wave atomizer. Sens Actuators A 145:437–441
Kalitzin G, Medic G, Iaccarino G, Durbin P (2005) Near-wall behavior of RANS turbulence models and implications for wall functions. J Comput Phys 204:265–291
Kamin W, Genz T, Roeder S, Scheuch G, Trammer T, Juenemann R, Cloes R (2002) Mass output and particle size distribution of glucocorticosteroids emitted from different inhalation devices depending on various inspiratory parameters. J Aerosol Med 15:65–73
Khilnani G, Banga A (2004) Aerosol therapy. J Indian Acad Clin Med 5:114–123
Kleinstreuer C, Shi H, Zhang Z (2007) Computational analyses of a pressurized metered dose inhaler and a new drug-aerosol targeting methodology. J Aerosol Med 20:294–309. doi:10.1089/jam.2006.0617
Kleinstreuer C, Zhang Z (2003a) Laminar-to-turbulent fluid–particle flows in a human airway model. Int J Multiph Flow 29:271–289
Kleinstreuer C, Zhang Z (2003b) Targeted drug aeroso deposition analysis for a four-generation lung airway model with hemispherical tumors. J Biomech Eng 125:197–206
Kleinstreuer C, Zhang Z (2010) Airflow and particle transport in the human respiratory system. Annu Rev Fluid Mech 42:301–334
Kleinstreuer C, Zhang Z, Donohue JF (2008) Targeted drug-aerosol delivery in the human respiratory system. Annu Rev Biomed Eng 10:195–220
Kofman C, Berlinski A, Zaragoza S, Teper A (2004) Aerosol therapy for pediatric outpatients. RT J Respir Care Pract 117:26–28
Kurosawa M, Watanabe T, Futami A, Higuchi T (1995) Surface acoustic wave atomizer. Sens Actuators A 50:69–74
Lambert AR, O’Shaughnessy PT, Tawhai MH, Hoffman EA, Lin C-L (2011) Regional deposition of particles in an image-based airway model: large-eddy simulation and left-right lung ventilation asymmetry. Aerosol Sci Technol 45:11–25. doi:10.1080/02786826.2010.517578
LaVan DA, Lynn DM, Langer R (2002) Moving smaller in drug discovery and delivery. Nat Rev Drug Discov 1:77–84
Lavorini F et al (2011) Retail sales of inhalation devices in European countries: so much for a global policy. Respir Med 105:1099–1103. doi:10.1016/j.rmed.2011.03.012
Li Z, Kleinstreuer C, Zhang Z (2007) Simulation of airflow fields and microparticle deposition in realistic human lung airway models. Part I: airflow patterns. Eur J Mech B/Fluids 26:632–649
Liu Y, So R, Zhang C (2002) Modeling the bifurcating flow in a human lung airway. J Biomech 35:465–473
Liu Y, So RM, Zhang CH (2003) Modeling the bifurcating flow in an asymmetric human lung airway. J Biomech 36:951–959
Longest PW, Xi J (2007) Computational investigation of particle inertia effects on submicron aerosol deposition in the respiratory tract. J Aerosol Sci 38:111–130. doi:10.1016/j.jaerosci.2006.09.007
Luo H, Liu Y (2008) Modeling the bifurcating flow in a CT-scanned human lung airway. J Biomech 41:2681–2688
Ma B, Lutchen KR (2006) An anatomically based hybrid computational model of the human lung and its application to low frequency oscillatory mechanics. Ann Biomed Eng 34:1691–1704
Molimard M, Raherison C, Lignot S, Depont F, Abouelfath A, Moore N (2003) Assessment of handling of inhaler devices in real life: an observational study in 3811 patients in primary care. J Aerosol Med 16:249–254. doi:10.1089/089426803769017613
Möller W, Meyer G, Scheuch G, Kreyling WG, Bennett WD (2009) Left-to-right asymmetry of aerosol deposition after shallow bolus inhalation depends on lung ventilation. J Aerosol Med Pulm Drug Deliv 22:333–339
Morsi S, Alexander A (1972) An investigation of particle trajectories in two-phase flow systems. J Fluid Mech 55:193–208
Newman SP (2004) Dry powder inhalers for optimal drug delivery. Expert Opin Biol ther 4:23–33. doi:10.1517/14712598.4.1.23
Nithiarasu P et al (2008) Steady flow through a realistic human upper airway geometry. Int J Numer Methods Fluids 57:631–651
Nowak N, Kakade PP, Annapragada AV (2003) Computational fluid dynamics simulation of airflow and aerosol deposition in human lungs. Ann Biomed Eng 31:374–390
O’Connor BJ (2004) The ideal inhaler: design and characteristics to improve outcomes. Respir Med 98(Suppl):S10–S16
Ounis H, Ahmadi G, McLaughlin JB (1991) Brownian diffusion of submicrometer particles in the viscous sublayer. J Colloid Interface Sci 143:266–277. doi:10.1016/0021-9797(91)90458-K
Pourmehran O, Gorji TB, Gorji-Bandpy M (2016) Magnetic drug targeting through a realistic model of human tracheobronchial airways using computational fluid and particle dynamics. Biomech Model Mechanobiol 15:1355–1374
Price D et al (2011) Device type and real-world effectiveness of asthma combination therapy: an observational study. Respir Med 105:1457–1466. doi:10.1016/j.rmed.2011.04.010
Qi A, Friend JR, Yeo LY, Morton DA, McIntosh MP, Spiccia L (2009) Miniature inhalation therapy platform using surface acoustic wave microfluidic atomization. Lab Chip 9:2184–2193
Qi A, Yeo LY, Friend JR (2008) Interfacial destabilization and atomization driven by surface acoustic waves (1994-present). Phys Fluids 20:074103
Rajapaksa AE et al (2014) Effective pulmonary delivery of an aerosolized plasmid DNA vaccine via surface acoustic wave nebulization. Respir Res 15:60
Razzacki SZ, Thwar PK, Yang M, Ugaz VM, Burns MA (2004) Integrated microsystems for controlled drug delivery. Adv Drug Deliv Rev 56:185–198
Ryval J, Straatman A, Steinman D (2004) Two-equation turbulence modeling of pulsatile flow in a stenosed tube. Trans ASME-K J Biomech Eng 126:625–635
Scheuch G, Kohlhaeufl MJ, Brand P, Siekmeier R (2006) Clinical perspectives on pulmonary systemic and macromolecular delivery. Adv Drug Deliv Rev 58:996–1008
Shi H, Kleinstreuer C, Zhang Z (2007) Modeling of inertial particle transport and deposition in human nasal cavities with wall roughness. J Aerosol Sci 38:398–419. doi:10.1016/j.jaerosci.2007.02.002
Smola M, Vandamme T, Sokolowski A (2008) Nanocarriers as pulmonary drug delivery systems to treat and to diagnose respiratory and non respiratory diseases. Int J Nanomed 3:1–19
Taburet A-M, Schmit B (1994) Pharmacokinetic optimisation of asthma treatment. Clin Pharmacokinet 26:396–418
Tandon R, McPeck M, Smaldone GC (1997) Measuring nebulizer output: aerosol production vs gravimetric analysis. Chest J 111:1361–1365
Theunissen R, Reithmuller ML (2008) Particle image velocimetry in lung bifurcation models. In: Particle image velocimetry, pp 73–101. doi:10.1007/978-3-540-73528-1_5
Tian L, Ahmadi G (2007) Particle deposition in turbulent duct flows–comparisons of different model predictions. J Aerosol Sci 38:377–397. doi:10.1016/j.jaerosci.2006.12.003
Van Oort M (1995) In vitro testing of dry powder inhalers. Aerosol Sci Technol 22:364–373. doi:10.1080/02786829408959754
Varghese SS, Frankel SH (2003) Numerical modeling of pulsatile turbulent flow in stenotic vessels. Trans AM Soc Mech Eng J Biomech Eng 125:445–460
Vidgren M, Arppe J, Vidgren P, Hyvarinen L, Vainio P, Silvasti M, Tukiainen H (1994) Pulmonary deposition and clinical-response of Tc-99m-labeled salbutamol delivered from a novel multiple-dose powder inhaler. Pharmaceut Res 11:1320–1324. doi:10.1023/A:1018902830192
Vincken W, Dekhuijzen PR, Barnes P, Group A (2010) The ADMIT series—issues in inhalation therapy. 4 How to choose inhaler devices for the treatment of COPD. Prim Care Respir J 19:10–20. doi:10.4104/pcrj.2009.00062
Virchow JC, Crompton GK, Dal Negro R, Pedersen S, Magnan A, Seidenberg J, Barnes PJ (2008) Importance of inhaler devices in the management of airway disease. Respir Med 102:10–19. doi:10.1016/j.rmed.2007.07.031
Wang Y, Rezk AR, Khara JS, Yeo LY, Ee PLR (2016) Stability and efficacy of synthetic cationic antimicrobial peptides nebulized using high frequency acoustic waves. Biomicrofluidics 10:034115
Weibel ER (1997) Design of airways and blood vessels considered as branching trees. In: Crystal RG, West JB, Weibel ER, Barnes PJ (eds) The lung: scientific foundations. Lippincott-Raven Publishers, Philadelphia, pp 1061–1071
Wen D, Zhang L, He Y (2009) Flow and migration of nanoparticle in a single channel. Heat Mass Transf 45:1061–1067. doi:10.1007/s00231-009-0479-8
Wilcox DC (1998) Turbulence modeling for CFD, vol 2. DCW Industries, La Canada
Winkler A, Harazim S, Menzel S, Schmidt H (2015) SAW-based fluid atomization using mass-producible chip devices. Lab Chip 15:3793–3799
Yang MY, Chan JG, Chan HK (2014) Pulmonary drug delivery by powder aerosols. J Control Release 193c:228–240. doi:10.1016/j.jconrel.2014.04.055
Yazdani A, Normandie M, Yousefi M, Saidi M, Ahmadi G (2014) Transport and deposition of pharmaceutical particles in three commercial spacer—MDI combinations. Comput Biol Med 54:145–155
Yeo LY, Friend JR (2014) Surface acoustic wave microfluidics. Annu Rev Fluid Mech 46:379–406
Yeo LY, Friend JR, McIntosh MP, Meeusen EN, Morton DA (2010) Ultrasonic nebulization platforms for pulmonary drug delivery. Expert Opin Drug Deliv 7:663–679
Yeo LY, Lastochkin D, Wang S-C, Chang H-C (2004) A new ac electrospray mechanism by Maxwell–Wagner polarization and capillary resonance. Phys Rev Lett 92:133902
Yousefi M, Inthavong K, Tu J (2015) Microparticle transport and deposition in the human oral airway: toward the smart spacer. Aerosol Sci Technol 49:1109–1120
Zhang Z, Kleinstreuer C (2002) Transient airflow structures and particle transport in a sequentially branching lung airway model. Phys Fluids 14:862–880
Zhang Z, Kleinstreuer C (2003) Low-Reynolds-number turbulent flows in locally constricted conduits: a comparison study. AIAA J 41:831–840
Zhang Z, Kleinstreuer C, Donohue JF, Kim C (2005) Comparison of micro-and nano-size particle depositions in a human upper airway model. J Aerosol Sci 36:211–233
Zhang Z, Kleinstreuer C, Kim CS (2002) Micro-particle transport and deposition in a human oral airway model. J Aerosol Sci 33:1635–1652. doi:10.1016/S0021-8502(02)00122-2
Zhou Y, Sun J, Cheng YS (2011) Comparison of deposition in the USP and physical mouth-throat models with solid and liquid particles. J Aerosol Med Pulm Drug Deliv 24:8
Acknowledgements
We acknowledge the support of this work from the Australian Government Research Training Program Scholarship and also to the Australian Research Council for a Future Fellowship (FT130100672).
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Yousefi, M., Pourmehran, O., Gorji-Bandpy, M. et al. CFD simulation of aerosol delivery to a human lung via surface acoustic wave nebulization. Biomech Model Mechanobiol 16, 2035–2050 (2017). https://doi.org/10.1007/s10237-017-0936-0
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DOI: https://doi.org/10.1007/s10237-017-0936-0