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Published in: Respiratory Research 1/2016

Open Access 01-12-2016 | Research

Micron-sized and submicron-sized aerosol deposition in a new ex vivo preclinical model

Authors: Sophie Perinel, Lara Leclerc, Nathalie Prévôt, Agathe Deville, Michèle Cottier, Marc Durand, Jean-Michel Vergnon, Jérémie Pourchez

Published in: Respiratory Research | Issue 1/2016

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Abstract

Background

The knowledge of where particles deposit in the respiratory tract is crucial for understanding the health effects associated with inhaled drug particles.

Method

An ex vivo study was conducted to assess regional deposition patterns (thoracic vs. extrathoracic) of radioactive polydisperse aerosols with different size ranges [0.15 μm–0.5 μm], [0.25 μm–1 μm] and [1 μm–9 μm]. SPECT/CT analyses were performed complementary in order to assess more precisely the regional deposition of aerosols within the pulmonary tract.
Experiments were set using an original respiratory tract model composed of a human plastinated head connected to an ex vivo porcine pulmonary tract. The model was ventilated by passive expansion, simulating pleural depressions. Aerosol was administered during nasal breathing.

Results

Planar scintigraphies allowed to calculate the deposited aerosol fractions for particles in the three size ranges from sub-micron to micron The deposited fractions obtained, for thoracic vs. extra-thoracic regions respectively, were 89 ± 4 % vs. 11 ± 4 % for [0.15 μm–0.5 μm], 78 ± 5 % vs. 22 ± 5 % for [0.25 μm–1 μm] and 35 ± 11 % vs.65 ± 11 % for [1 μm–9 μm].

Conclusion

Results obtained with this new ex vivo respiratory tract model are in good agreement with the in vivo data obtained in studies with baboons and humans.
Literature
1.
go back to reference Kannan R, Guo P, Przekwas A. Particle transport in the human respiratory tract: formulation of a nodal inverse distance weighted Eulerian–Lagrangian transport and implementation of the Wind–Kessel algorithm for an oral delivery. Int J Numer Methods Biomed Eng. 2016;32. Kannan R, Guo P, Przekwas A. Particle transport in the human respiratory tract: formulation of a nodal inverse distance weighted Eulerian–Lagrangian transport and implementation of the Wind–Kessel algorithm for an oral delivery. Int J Numer Methods Biomed Eng. 2016;32.
2.
go back to reference Löndahl J, Möller W, Pagels JH, Kreyling WG, Swietlicki E, Schmid O. Measurement techniques for respiratory tract deposition of airborne nanoparticles: a critical review. J Aerosol Med Pulm Drug Deliv. 2013;27:229–54.CrossRefPubMed Löndahl J, Möller W, Pagels JH, Kreyling WG, Swietlicki E, Schmid O. Measurement techniques for respiratory tract deposition of airborne nanoparticles: a critical review. J Aerosol Med Pulm Drug Deliv. 2013;27:229–54.CrossRefPubMed
3.
go back to reference Daigle CC, Chalupa DC, Gibb FR, Morrow PE, Oberdörster G, Utell MJ, et al. Ultrafine particle deposition in humans during rest and exercise. Inhal Toxicol. 2003;15:539–52.CrossRefPubMed Daigle CC, Chalupa DC, Gibb FR, Morrow PE, Oberdörster G, Utell MJ, et al. Ultrafine particle deposition in humans during rest and exercise. Inhal Toxicol. 2003;15:539–52.CrossRefPubMed
4.
go back to reference Laube BL. In vivo measurements of aerosol dose and distribution: clinical relevance. J Aerosol Med Off J Int Soc Aerosols Med. 1996;9 Suppl 1:S77–91. Laube BL. In vivo measurements of aerosol dose and distribution: clinical relevance. J Aerosol Med Off J Int Soc Aerosols Med. 1996;9 Suppl 1:S77–91.
5.
go back to reference McKinney W, Jackson M, Sager TM, Reynolds JS, Chen BT, Afshari A, et al. Pulmonary and cardiovascular responses of rats to inhalation of a commercial antimicrobial spray containing titanium dioxide nanoparticles. Inhal Toxicol. 2012;24:447–57.CrossRefPubMedPubMedCentral McKinney W, Jackson M, Sager TM, Reynolds JS, Chen BT, Afshari A, et al. Pulmonary and cardiovascular responses of rats to inhalation of a commercial antimicrobial spray containing titanium dioxide nanoparticles. Inhal Toxicol. 2012;24:447–57.CrossRefPubMedPubMedCentral
6.
go back to reference Oosthuizen MA, Oberholzer HM, Scriba MR, van der Spuy WJ, Pretorius E. Evaluation of the morphological changes in the lungs of BALB/c mice after inhalation of spherical and rod-shaped titanium nanoparticles. Micron Oxf Engl. 2012;43:863–9. Oosthuizen MA, Oberholzer HM, Scriba MR, van der Spuy WJ, Pretorius E. Evaluation of the morphological changes in the lungs of BALB/c mice after inhalation of spherical and rod-shaped titanium nanoparticles. Micron Oxf Engl. 2012;43:863–9.
7.
go back to reference Kuempel ED, Tran CL, Castranova V, Bailer AJ. Lung dosimetry and risk assessment of nanoparticles: evaluating and extending current models in rats and humans. Inhal Toxicol. 2006;18:717–24.CrossRefPubMed Kuempel ED, Tran CL, Castranova V, Bailer AJ. Lung dosimetry and risk assessment of nanoparticles: evaluating and extending current models in rats and humans. Inhal Toxicol. 2006;18:717–24.CrossRefPubMed
8.
go back to reference Awadalla M, Miyawaki S, Abou Alaiwa MH, Adam RJ, Bouzek DC, Michalski AS, et al. Early airway structural changes in cystic fibrosis pigs as a determinant of particle distribution and deposition. Ann Biomed Eng. 2014;42:915–27.CrossRefPubMed Awadalla M, Miyawaki S, Abou Alaiwa MH, Adam RJ, Bouzek DC, Michalski AS, et al. Early airway structural changes in cystic fibrosis pigs as a determinant of particle distribution and deposition. Ann Biomed Eng. 2014;42:915–27.CrossRefPubMed
9.
go back to reference Ford WR, Blair AE, Evans RL, John E, Bugert JJ, Broadley KJ, et al. Human parainfluenza type 3 virus impairs the efficacy of glucocorticoids to limit allergy-induced pulmonary inflammation in guinea-pigs. Clin Sci Lond Engl 1979. 2013;125:471–82. Ford WR, Blair AE, Evans RL, John E, Bugert JJ, Broadley KJ, et al. Human parainfluenza type 3 virus impairs the efficacy of glucocorticoids to limit allergy-induced pulmonary inflammation in guinea-pigs. Clin Sci Lond Engl 1979. 2013;125:471–82.
10.
go back to reference Manunta MDI, McAnulty RJ, McDowell A, Jin J, Ridout D, Fleming J, et al. Airway deposition of nebulized gene delivery nanocomplexes monitored by radioimaging agents. Am J Respir Cell Mol Biol. 2013;49:471–80.CrossRefPubMedPubMedCentral Manunta MDI, McAnulty RJ, McDowell A, Jin J, Ridout D, Fleming J, et al. Airway deposition of nebulized gene delivery nanocomplexes monitored by radioimaging agents. Am J Respir Cell Mol Biol. 2013;49:471–80.CrossRefPubMedPubMedCentral
11.
go back to reference Albuquerque-Silva I, Vecellio L, Durand M, Avet J, Le Pennec D, de Monte M, et al. Particle deposition in a child respiratory tract model: in vivo regional deposition of fine and ultrafine aerosols in baboons. PLoS One. 2014;9:e95456.CrossRefPubMedPubMedCentral Albuquerque-Silva I, Vecellio L, Durand M, Avet J, Le Pennec D, de Monte M, et al. Particle deposition in a child respiratory tract model: in vivo regional deposition of fine and ultrafine aerosols in baboons. PLoS One. 2014;9:e95456.CrossRefPubMedPubMedCentral
12.
go back to reference Durand M, Pourchez J, Louis B, Pouget JF, Isabey D, Coste A, et al. Plastinated nasal model: a new concept of anatomically realistic cast. Rhinology. 2011;49:30–6.PubMed Durand M, Pourchez J, Louis B, Pouget JF, Isabey D, Coste A, et al. Plastinated nasal model: a new concept of anatomically realistic cast. Rhinology. 2011;49:30–6.PubMed
13.
go back to reference Leclerc L, Pourchez J, Prevot N, Vecellio L, Le Guellec S, Cottier M, et al. Assessing sinus aerosol deposition: Benefits of SPECT–CT imaging. Int J Pharm. 2014;462:135–41.CrossRefPubMed Leclerc L, Pourchez J, Prevot N, Vecellio L, Le Guellec S, Cottier M, et al. Assessing sinus aerosol deposition: Benefits of SPECT–CT imaging. Int J Pharm. 2014;462:135–41.CrossRefPubMed
14.
go back to reference Le Guellec S, Le Pennec D, Gatier S, Leclerc L, Cabrera M, Pourchez J, et al. Validation of anatomical models to study aerosol deposition in human nasal cavities. Pharm Res. 2014;31:228–37.CrossRefPubMed Le Guellec S, Le Pennec D, Gatier S, Leclerc L, Cabrera M, Pourchez J, et al. Validation of anatomical models to study aerosol deposition in human nasal cavities. Pharm Res. 2014;31:228–37.CrossRefPubMed
15.
go back to reference Durand M, Rusch P, Granjon D, Chantrel G, Prades JM, Dubois F, et al. Preliminary study of the deposition of aerosol in the maxillary sinuses using a plastinated model. J Aerosol Med Off J Int Soc Aerosols Med. 2001;14:83–93.CrossRef Durand M, Rusch P, Granjon D, Chantrel G, Prades JM, Dubois F, et al. Preliminary study of the deposition of aerosol in the maxillary sinuses using a plastinated model. J Aerosol Med Off J Int Soc Aerosols Med. 2001;14:83–93.CrossRef
16.
go back to reference Durand M, Pourchez J, Aubert G, Le Guellec S, Navarro L, Forest V, et al. Impact of acoustic airflow nebulization on intrasinus drug deposition of a human plastinated nasal cast: new insights into the mechanisms involved. Int J Pharm. 2011;421:63–71.CrossRefPubMed Durand M, Pourchez J, Aubert G, Le Guellec S, Navarro L, Forest V, et al. Impact of acoustic airflow nebulization on intrasinus drug deposition of a human plastinated nasal cast: new insights into the mechanisms involved. Int J Pharm. 2011;421:63–71.CrossRefPubMed
17.
go back to reference Durand M, Le Guellec S, Pourchez J, Dubois F, Aubert G, Chantrel G, et al. Sonic aerosol therapy to target maxillary sinuses. Eur Ann Otorhinolaryngol Head Neck Dis. 2012;129:244–50.CrossRefPubMed Durand M, Le Guellec S, Pourchez J, Dubois F, Aubert G, Chantrel G, et al. Sonic aerosol therapy to target maxillary sinuses. Eur Ann Otorhinolaryngol Head Neck Dis. 2012;129:244–50.CrossRefPubMed
18.
go back to reference Leclerc L, Pourchez J, Aubert G, Leguellec S, Vecellio L, Cottier M, et al. Impact of Airborne Particle Size, Acoustic Airflow and Breathing Pattern on Delivery of Nebulized Antibiotic into the Maxillary Sinuses Using a Realistic Human Nasal Replica. Pharm Res. 2014;31:2335–43.CrossRefPubMed Leclerc L, Pourchez J, Aubert G, Leguellec S, Vecellio L, Cottier M, et al. Impact of Airborne Particle Size, Acoustic Airflow and Breathing Pattern on Delivery of Nebulized Antibiotic into the Maxillary Sinuses Using a Realistic Human Nasal Replica. Pharm Res. 2014;31:2335–43.CrossRefPubMed
19.
go back to reference Leclerc L, Merhie AE, Navarro L, Prévôt N, Durand M, Pourchez J. Impact of acoustic airflow on intrasinus drug deposition: New insights into the vibrating mode and the optimal acoustic frequency to enhance the delivery of nebulized antibiotic. Int J Pharm. 2015;494:227–34.CrossRefPubMed Leclerc L, Merhie AE, Navarro L, Prévôt N, Durand M, Pourchez J. Impact of acoustic airflow on intrasinus drug deposition: New insights into the vibrating mode and the optimal acoustic frequency to enhance the delivery of nebulized antibiotic. Int J Pharm. 2015;494:227–34.CrossRefPubMed
20.
go back to reference Perinel S, Pourchez J, Leclerc L, Avet J, Durand M, Prévôt N, et al. An ex vivo chimeric human-porcine preclinical model for aerosol deposition studies. 2015. In Press Perinel S, Pourchez J, Leclerc L, Avet J, Durand M, Prévôt N, et al. An ex vivo chimeric human-porcine preclinical model for aerosol deposition studies. 2015. In Press
21.
go back to reference Merhie AE, Navarro L, Delavenne X, Leclerc L, Pourchez J. A new Strategy to Improve Drug Delivery to the Maxillary Sinuses: The Frequency Sweep Acoustic Airflow. Pharm Res. 2016;33(5)1074–84.CrossRefPubMed Merhie AE, Navarro L, Delavenne X, Leclerc L, Pourchez J. A new Strategy to Improve Drug Delivery to the Maxillary Sinuses: The Frequency Sweep Acoustic Airflow. Pharm Res. 2016;33(5)1074–84.CrossRefPubMed
22.
go back to reference Moller W, Saba GK, Haussinger K, Becker S, Keller M, Schuschnig U. Nasally inhaled pulsating aerosols: lung, sinus and nose deposition. Rhinology. 2011;49:286–91.PubMed Moller W, Saba GK, Haussinger K, Becker S, Keller M, Schuschnig U. Nasally inhaled pulsating aerosols: lung, sinus and nose deposition. Rhinology. 2011;49:286–91.PubMed
23.
go back to reference Booker R. Interpretation and evaluation of pulmonary function tests. Nurs Stand R Coll Nurs G B 1987. 2009;23:46–56. quiz 58. Booker R. Interpretation and evaluation of pulmonary function tests. Nurs Stand R Coll Nurs G B 1987. 2009;23:46–56. quiz 58.
24.
go back to reference Criée CP, Sorichter S, Smith HJ, Kardos P, Merget R, Heise D, et al. Body plethysmography – Its principles and clinical use. Respir Med. 2011;105:959–71.CrossRefPubMed Criée CP, Sorichter S, Smith HJ, Kardos P, Merget R, Heise D, et al. Body plethysmography – Its principles and clinical use. Respir Med. 2011;105:959–71.CrossRefPubMed
25.
go back to reference Flesch JD, Dine CJ. Lung volumes: Measurement, clinical use, and coding. CHEST J. 2012;142:506–10.CrossRef Flesch JD, Dine CJ. Lung volumes: Measurement, clinical use, and coding. CHEST J. 2012;142:506–10.CrossRef
26.
go back to reference Grgic B, Finlay WH, Burnell PKP, Heenan AF. In vitro intersubject and intrasubject deposition measurements in realistic mouth–throat geometries. J Aerosol Sci. 2004;35:1025–40.CrossRef Grgic B, Finlay WH, Burnell PKP, Heenan AF. In vitro intersubject and intrasubject deposition measurements in realistic mouth–throat geometries. J Aerosol Sci. 2004;35:1025–40.CrossRef
27.
go back to reference Ibrahim Z, Busch J, Awwad M, Wagner R, Wells K, Cooper DKC. Selected physiologic compatibilities and incompatibilities between human and porcine organ systems. Xenotransplantation. 2006;13:488–99.CrossRefPubMed Ibrahim Z, Busch J, Awwad M, Wagner R, Wells K, Cooper DKC. Selected physiologic compatibilities and incompatibilities between human and porcine organ systems. Xenotransplantation. 2006;13:488–99.CrossRefPubMed
28.
go back to reference West JB. L’essentiel sur la physiologie respiratoire. Essent. Sur Physiol. Respir. 6° édition. Paris, France: EDISEM-MALOINE; 2003. West JB. L’essentiel sur la physiologie respiratoire. Essent. Sur Physiol. Respir. 6° édition. Paris, France: EDISEM-MALOINE; 2003.
29.
go back to reference Clark AR. MDIs: Physics of Aerosol Formation. J Aerosol Med. 1996;9:S–19.CrossRef Clark AR. MDIs: Physics of Aerosol Formation. J Aerosol Med. 1996;9:S–19.CrossRef
31.
go back to reference Crowe CT, Schwarzkopf JD, Sommerfeld M, Tsuji Y. Multiphase Flows with Droplets and Particles, Second Edition. 2 edition. Paris, France: CRC Press; 2011. Crowe CT, Schwarzkopf JD, Sommerfeld M, Tsuji Y. Multiphase Flows with Droplets and Particles, Second Edition. 2 edition. Paris, France: CRC Press; 2011.
32.
go back to reference Crowe CT, Elger DF, Roberson JA. Engineering Fluid Mechanics. 8 edition. Paris, France: Wiley; 2006. Crowe CT, Elger DF, Roberson JA. Engineering Fluid Mechanics. 8 edition. Paris, France: Wiley; 2006.
33.
go back to reference Darquenne C, Fleming JS, Katz I, Martin AR, Schroeter J, Usmani OS, et al. Bridging the gap between science and clinical efficacy: physiology, imaging, and modeling of aerosols in the lung. J Aerosol Med Pulm Drug Deliv. 2016;29:107–26.CrossRefPubMed Darquenne C, Fleming JS, Katz I, Martin AR, Schroeter J, Usmani OS, et al. Bridging the gap between science and clinical efficacy: physiology, imaging, and modeling of aerosols in the lung. J Aerosol Med Pulm Drug Deliv. 2016;29:107–26.CrossRefPubMed
34.
go back to reference Sá RC, Zeman KL, Bennett WD, Prisk GK, Darquenne C. Effect of posture on regional deposition of coarse particles in the healthy human lung. J Aerosol Med Pulm Drug Deliv. 2015;28(6):423–31.CrossRefPubMed Sá RC, Zeman KL, Bennett WD, Prisk GK, Darquenne C. Effect of posture on regional deposition of coarse particles in the healthy human lung. J Aerosol Med Pulm Drug Deliv. 2015;28(6):423–31.CrossRefPubMed
36.
go back to reference Becquemin MH, Swift DL, Bouchikhi A, Roy M, Teillac A. Particle deposition and resistance in the noses of adults and children. Eur Respir J. 1991;4:694–702.PubMed Becquemin MH, Swift DL, Bouchikhi A, Roy M, Teillac A. Particle deposition and resistance in the noses of adults and children. Eur Respir J. 1991;4:694–702.PubMed
37.
go back to reference Becquemin MH, Roy M, Robeau D, Bonnefous S, Piechowski J, Teillac A. Inhaled particle deposition and clearance from the normal respiratory tract. Respir Physiol. 1987;67:147–58.CrossRefPubMed Becquemin MH, Roy M, Robeau D, Bonnefous S, Piechowski J, Teillac A. Inhaled particle deposition and clearance from the normal respiratory tract. Respir Physiol. 1987;67:147–58.CrossRefPubMed
Metadata
Title
Micron-sized and submicron-sized aerosol deposition in a new ex vivo preclinical model
Authors
Sophie Perinel
Lara Leclerc
Nathalie Prévôt
Agathe Deville
Michèle Cottier
Marc Durand
Jean-Michel Vergnon
Jérémie Pourchez
Publication date
01-12-2016
Publisher
BioMed Central
Published in
Respiratory Research / Issue 1/2016
Electronic ISSN: 1465-993X
DOI
https://doi.org/10.1186/s12931-016-0395-7

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