In vitro, in vivo and ex vivo models for studying particle deposition and drug absorption of inhaled pharmaceuticals

European Journal of Pharmaceutical Sciences

Volumn 49, Issue 5, 2013, Pages 805-818

  Nahar, Kamrun ^a   Gupta, Nilesh ^a   Gauvin, Robert ^b,c,d,e   Absar, Shahriar ^a   Patel, Brijeshkumar ^a   Gupta, Vivek ^a,f   Khademhosseini, Ali ^b,c,d   Ahsan, Fakhrul ^a  

^a TEXAS TECH UNIVERSITY HEALTH SCIENCES CENTER   (United States)

^b HARVARD MIT DIVISION OF HEALTH SCIENCES AND TECHNOLOGY   (United States)

^c BRIGHAM AND WOMEN S HOSPITAL   (United States)

^d HARVARD MEDICAL SCHOOL   (United States)

^e Quebec Center for Functional Materials   (Canada)

^f Santa Barbara   (United States)

Author keywords

Drug absorption from lung; Imaging; In vitro models; Isolated perfused lung; Particle deposition; Pulmonary drug delivery

Indexed keywords

BUDESONIDE; RESPIRATORY TRACT AGENT;

AIRBORNE PARTICLE; ARTICLE; CELL CULTURE; DRUG ABSORPTION; DRUG DELIVERY SYSTEM; ELECTRIC RESISTANCE; FLUORESCENCE IMAGING; GAMMA SCINTIGRAPHY; HUMAN; IN VITRO STUDY; IN VIVO STUDY; INHALATION; INHALER; LUNG MODEL; NONHUMAN; NUCLEAR MAGNETIC RESONANCE IMAGING; PARTICLE SIZE; POSITIVE END EXPIRATORY PRESSURE; POSITRON EMISSION TOMOGRAPHY; PRIORITY JOURNAL; RESPIRATORY EPITHELIUM; SINGLE PHOTON EMISSION COMPUTER TOMOGRAPHY; WETTABILITY;

EID: 84885042493     PISSN: 09280987     EISSN: 18790720     Source Type: Journal    
DOI: 10.1016/j.ejps.2013.06.004     Document Type: Review

References (175)

1. Adams, K.E., Ke, S., Kwon, S., Liang, F., Fan, Z., Lu, Y., Hirschi, K., Mawad, M.E., Barry, M.A., Sevick-Muraca, E.M., 2007. Comparison of visible and near-infrared wavelength-excitable fluorescent dyes for molecular imaging of cancer. J. Biomed. Opt. 12, 024017.
2. Ahsan, F., Arnold, J.J., Meezan, E., Pillion, D.J., 2001. Mutual inhibition of the insulin absorption-enhancing properties of dodecylmaltoside and dimethyl-betacyclodextrin following nasal administration. Pharm. Res. 18, 608-614. (Pubitemid 32595788)
3. Ahsan, F., Arnold, J.J., Yang, T., Meezan, E., Schwiebert, E.M., Pillion, D.J., 2003. Effects of the permeability enhancers, tetradecylmaltoside and dimethyl-betacyclodextrin, on insulin movement across human bronchial epithelial cells (16HBE14o-). Eur. J. Pharm. Sci. 20, 27-34. (Pubitemid 37103229)
4. Al-Qadi, S., Grenha, A., Carrion-Recio, D., Seijo, B., Remunan-Lopez, C., 2012. Microencapsulated chitosan nanoparticles for pulmonary protein delivery: in vivo evaluation of insulin-loaded formulations. J. Control. Release 157, 383-390.
5. Bai, S., Ahsan, F., 2009. Synthesis and evaluation of pegylated dendrimeric nanocarrier for pulmonary delivery of low molecular weight heparin. Pharm. Res. 26, 539-548.
6. Bai, S., Ahsan, F., 2010. Inhalable liposomes of low molecular weight heparin for the treatment of venous thromboembolism. J. Pharm. Sci. 99, 4554-4564.
7. Bai, S., Gupta, V., Ahsan, F., 2010. Inhalable lactose-based dry powder formulations of low molecular weight heparin. J. Aerosol Med. Pulm. Drug Deliv. 23, 97-104.
8. Ben Jebria, A., Tabka, Z., Techoueyres, P., 1987. Steady pressure-flow relationship in a cast of the upper and central human airways. Int. J. Biomed. Comput. 20, 211-224. (Pubitemid 17042609)
9. Bennett, W.D., Scheuch, G., Zeman, K.L., Brown, J.S., 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. (Pubitemid 29046954)
10. Bi, R., Shao, W., Wang, Q., Zhang, N., 2009. Solid lipid nanoparticles as insulin inhalation carriers for enhanced pulmonary delivery. J. Biomed. Nanotechnol. 5, 84-92.
11. Bleyl, J.U., Heller, A.R., Fehrenbach, A., Heintz, M., Fehrenbach, H., Klenz, G., Gama de Abreu, M., Hubler, M., Spieth, P.M., Koch, T., 2010. Pretreatment with perfluorohexane vapor attenuates fMLP-induced lung injury in isolated perfused rabbit lungs. Exp. Lung Res. 36, 342-351.
12. Briot, R., Frank, J.A., Uchida, T., Lee, J.W., Calfee, C.S., Matthay, M.A., 2009. Elevated levels of the receptor for advanced glycation end products, a marker of alveolar epithelial type I cell injury, predict impaired alveolar fluid clearance in isolated perfused human lungs. Chest 135, 269-275.
13. Burton, J.A., Schanker, L.S., 1974. Absorption of sulphonamides and antitubercular drugs from the rat lung. Xenobiotica 4, 291-296.
14. Byron, P.R., Niven, R.W., 1988. A novel dosing method for drug administration to the airways of the isolated perfused rat lung. J. Pharm. Sci. 77, 693-695. (Pubitemid 19030293)
15. Byron, P.R., Roberts, N.S., Clark, A.R., 1986. An isolated perfused rat lung preparation for the study of aerosolized drug deposition and absorption. J. Pharm. Sci. 75, 168-171. (Pubitemid 16162541)
16. Byron, P.R., Hindle, M., Lange, C.F., Longest, P.W., McRobbie, D., Oldham, M.J., Olsson, B., Thiel, C.G., Wachtel, H., Finlay, W.H., 2010. In vivo-in vitro correlations: predicting pulmonary drug deposition from pharmaceutical aerosols. J. Aerosol Med. Pulm. Drug Deliv. 23 (Suppl. 2), S59-69.
17. Cannon, W.C., Blanton, E.F., McDonald, K.E., 1983. The flow-past chamber: an improved nose-only exposure system for rodents. Am. Ind. Hyg. Assoc. J. 44, 923-928. (Pubitemid 14177443)
18. Carvalho, T.C., Peters, J.I., Williams 3rd, R.O., 2011. Influence of particle size on regional lung deposition - what evidence is there? Int. J. Pharm. 406, 1-10.
19. Cavet, M.E., West, M., Simmons, N.L., 1997. Transepithelial transport of the fluoroquinolone ciprofloxacin by human airway epithelial Calu-3 cells. Antimicrob. Agents Chemother. 41, 2693-2698. (Pubitemid 27524741)
20. Chen, X., Huang, W., Wong, B.C., Yin, L., Wong, Y.F., Xu, M., Yang, Z., 2012. Liposomes prolong the therapeutic effect of anti-asthmatic medication via pulmonary delivery. Int. J. Nanomed. 7, 1139-1148.
21. Cheng, Y.S., Bowen, L., Rando, R.J., Postlethwait, E.M., Squadrito, G.L., Matalon, S., 2010. Exposing animals to oxidant gases: nose only vs. whole body. Proc. Am. Thorac. Soc. 7, 264-268.
22. Chengalvala, M., Lubeck, M.D., Davis, A.R., Mizutani, S., Molnar-Kimber, K., Morin, J., Hung, P.P., 1991. Evaluation of adenovirus type 4 and type 7 recombinant hepatitis B vaccines in dogs. Vaccine 9, 485-490.
23. Cherry, S.R., Gambhir, S.S., 2001. Use of positron emission tomography in animal research. Ilar. J. 42, 219-232. (Pubitemid 33708710)
24. Chiang, C.H., Chuang, C.H., Liu, S.L., Chian, C.F., Zhang, H., Ryu, J.H., 2012. Nacetylcysteine attenuates ventilator-induced lung injury in an isolated and perfused rat lung model. Injury 43, 1257-1263.
25. Comsa, D.C., Farrell, T.J., Patterson, M.S., 2008. Quantitative fluorescence imaging of point-like sources in small animals. Phys. Med. Biol. 53, 5797-5814.
26. Conway, J., 2012. Lung imaging - two dimensional gamma scintigraphy, SPECT, CT and PET. Adv. Drug Deliv. Rev. 64, 357-368.
27. Cryan, S.A., Sivadas, N., Garcia-Contreras, L., 2007. In vivo animal models for drug delivery across the lung mucosal barrier. Adv. Drug Deliv. Rev. 59, 1133-1151. (Pubitemid 47628783)
28. Cypel, M., Keshavjee, S., 2012. Isolated lung perfusion. Front Biosci. (Elite Ed). 4, 2226-2232.
29. de Boer, A.H., Gjaltema, D., Hagedoorn, P., Frijlink, H.W., 2002. Characterization of inhalation aerosols: a critical evaluation of cascade impactor analysis and laser diffraction technique. Int. J. Pharm. 249, 219-231. (Pubitemid 35333448)
30. De Marzo, N., Di Blasi, P., Boschetto, P., Mapp, C.E., Sartore, S., Picotti, G., Fabbri, L.M., 1989. Airway smooth muscle biochemistry and asthma. Eur. Respir. J. Suppl. 6, 473s-476s. (Pubitemid 19220435)
31. de Rochefort, L., Liu, T., Kressler, B., Liu, J., Spincemaille, P., Lebon, V., Wu, J., Wang, Y., 2010. Quantitative susceptibility map reconstruction from MR phase data using bayesian regularization: validation and application to brain imaging. Magn. Reson. Med. 63, 194-206.
32. Dolovich, M.B., 2009. 18F-fluorodeoxyglucose positron emission tomographic imaging of pulmonary functions, pathology, and drug delivery. Proc. Am. Thorac. Soc. 6, 477-485.
33. Dorato, M.A., 1990. Overview of inhalation toxicology. Environ. Health Perspect. 85, 163-170. (Pubitemid 20315296)
34. Dugas, H.L., Peters, J.I., Williams 3rd, R.O., 2013. Nebulization of mycophenolate mofetil inhalation suspension in rats: comparison with oral and pulmonary administration of cellcept(R). Int. J. Pharm. 441, 19-29.
35. Dunbar, C., Mitchell, J., 2005. Analysis of cascade impactor mass distributions. J. Aerosol. Med. 18, 439-451. (Pubitemid 43038409)
36. Dunbar, C., Kataya, A., Tiangbe, T., 2005. Reducing bounce effects in the Andersen cascade impactor. Int. J. Pharm. 301, 25-32. (Pubitemid 41206587)
37. Edwards, D.A., Hanes, J., Caponetti, G., Hrkach, J., Ben-Jebria, A., Eskew, M.L., Mintzes, J., Deaver, D., Lotan, N., Langer, R., 1997. Large porous particles for pulmonary drug delivery. Science 276, 1868-1871. (Pubitemid 27443665)
38. Effros, R.M., Mason, G.R., 1983. Measurements of pulmonary epithelial permeability in vivo. Am. Rev. Respir. Dis. 127, S59-65. (Pubitemid 13103650)
39. Enna, S.J., Schanker, L.S., 1972a. Absorption of drugs from the rat lung. Am. J. Physiol. 223, 1227-1231.
40. Enna, S.J., Schanker, L.S., 1972b. Absorption of saccharides and urea from the rat lung. Am. J. Physiol. 222, 409-414.
41. Everard, M.L., 1994. Studies using radiolabelled aerosols in children. Thorax 49, 1259-1266.
42. Ewing, P., Blomgren, B., Ryrfeldt, A., Gerde, P., 2006. Increasing exposure levels cause an abrupt change in the absorption and metabolism of acutely inhaled benzo(a)pyrene in the isolated, ventilated, and perfused lung of the rat. Toxicol. Sci. 91, 332-340. (Pubitemid 43827286)
43. Ewing, P., Eirefelt, S.J., Andersson, P., Blomgren, A., Ryrfeldt, A., Gerde, P., 2008. Short inhalation exposures of the isolated and perfused rat lung to respirable dry particle aerosols; the detailed pharmacokinetics of budesonide, formoterol, and terbutaline. J. Aerosol Med. Pulm. Drug Deliv. 21, 169-180.
44. Ewing, P., Ryrfeldt, A., Sjoberg, C.O., Andersson, P., Edsbacker, S., Gerde, P., 2010. Vasoconstriction after inhalation of budesonide: a study in the isolated and perfused rat lung. Pulm. Pharmacol. Ther. 23, 9-14.
45. Feddah, M.R., Brown, K.F., Gipps, E.M., Davies, N.M., 2000. In-vitro characterisation of metered dose inhaler versus dry powder inhaler glucocorticoid products: influence of inspiratory flow rates. J. Pharm. Pharm. Sci. 3, 318-324.
46. Ferron, G.A., 1994. Aerosol properties and lung deposition. Eur. Respir. J. 7, 1392-1394.
47. Flecknell, P., 2002. Replacement, reduction and refinement. Altex 19, 73-78.
48. Fleming, J., Conway, J., Majoral, C., Tossici-Bolt, L., Katz, I., Caillibotte, G., Perchet, D., Pichelin, M., Muellinger, B., Martonen, T., Kroneberg, P., Apiou-Sbirlea, G., 2011. The use of combined single photon emission computed tomography and X-ray computed tomography to assess the fate of inhaled aerosol. J. Aerosol Med. Pulm. Drug Deliv. 24, 49-60.
49. Forbes, B., Ehrhardt, C., 2005. Human respiratory epithelial cell culture for drug delivery applications. Eur. J. Pharm. Biopharm. e.V. 60, 193-205. (Pubitemid 40804561)
50. Garcia-Contreras, L., Sethuraman, V., Kazantseva, M., Godfrey, V., Hickey, A.J., 2006. Evaluation of dosing regimen of respirable rifampicin biodegradable microspheres in the treatment of tuberculosis in the guinea pig. J. Antimicrob. Chemother. 58, 980-986.
51. Gardner, S.F., Green, J.A., Bednarczyk, E.M., Farnett, L., Miraldi, F., 1992. Principles and clinical applications of positron emission tomography. Am. J. Hosp. Pharm. 49, 1499-1506.
52. Gerde, P., Ewing, P., Lastbom, L., Ryrfeldt, A., Waher, J., Liden, G., 2004. A novel method to aerosolize powder for short inhalation exposures at high concentrations: isolated rat lungs exposed to respirable diesel soot. Inhal. Toxicol. 16, 45-52. (Pubitemid 38101401)
53. Gettinger, S., 2008. Targeted therapy in advanced non-small-cell lung cancer. Semin. Respir. Crit. Care Med. 29, 291-301. (Pubitemid 351748435)
54. Gonda, I., 2000. The ascent of pulmonary drug delivery. J. Pharm. Sci. 89, 940-945.
55. Gupta, V., Ahsan, F., 2011. Influence of PEI as a core modifying agent on PLGA microspheres of PGE(1), a pulmonary selective vasodilator. Int. J. Pharm. 413, 51-62.
56. Gupta, V., Davis, M., Hope-Weeks, L.J., Ahsan, F., 2011a. PLGA microparticles encapsulating prostaglandin E1-hydroxypropyl-beta-cyclodextrin (PGE1-HPbetaCD) complex for the treatment of pulmonary arterial hypertension (PAH). Pharm. Res. 28, 1733-1749.
57. Haj, R.M., Cinco, J.E., Mazer, C.D., 2006. Treatment of pulmonary hypertension with selective pulmonary vasodilators. Curr. Opin Anaesthesiol. 19, 88-95. (Pubitemid 43269482)
58. Hamishehkar, H., Emami, J., Najafabadi, A.R., Gilani, K., Minaiyan, M., Hassanzadeh, K., Mahdavi, H., Koohsoltani, M., Nokhodchi, A., 2010. Pharmacokinetics and pharmacodynamics of controlled release insulin loaded PLGA microcapsules using dry powder inhaler in diabetic rats. Biopharm. Drug Dispos. 31, 189-201.
59. Harkema, J.R., Carey, S.A., Wagner, J.G., 2006. The nose revisited: a brief review of the comparative structure, function, and toxicologic pathology of the nasal epithelium. Toxicol. Pathol. 34, 252-269.
60. Hindle, M., Longest, P.W., 2012. Condensational growth of combination drugexcipient submicrometer particles for targeted high-efficiency pulmonary delivery: evaluation of formulation and delivery device. J. Pharm. Pharmacol. 64, 1254-1263.
61. Hojo, T., 1993. Scanning electron microscopy of styrene-methylethylketone casts of the airway and the arterial system of the lung. Scan. Microsc. 7, 287-293. (Pubitemid 23138234)
62. Huang, Y.Y., Wang, C.H., 2006. Pulmonary delivery of insulin by liposomal carriers. J. Control. Release 113, 9-14.
63. Huchon, G.J., Montgomery, A.B., Lipavsky, A., Hoeffel, J.M., Murray, J.F., 1987. Respiratory clearance of aerosolized radioactive solutes of varying molecular weight. J. Nucl. Med. 28, 894-902. (Pubitemid 17091530)
64. Hussain, A., Ahsan, F., 2006. Indication of transcytotic movement of insulin across human bronchial epithelial cells. J. Drug Target. 14, 181-190.
65. Jantzen, K., Roursgaard, M., Desler, C., Loft, S., Rasmussen, L.J., Moller, P., 2012. Oxidative damage to DNA by diesel exhaust particle exposure in co-cultures of human lung epithelial cells and macrophages. Mutagenesis 27, 693-701.
66. Jaques, P.A., Kim, C.S., 2000. Measurement of total lung deposition of inhaled ultrafine particles in healthy men and women. Inhal. Toxicol. 12, 715-731.
67. Kamiya, A., Sakagami, M., Byron, P.R., 2009. Cascade impactor practice for a high dose dry powder inhaler at 90 L/min: NGI versus modified 6-stage and 8-stage ACI. J. Pharm. Sci. 98, 1028-1039.
68. Klein, S.G., Hennen, J., Serchi, T., Blomeke, B., Gutleb, A.C., 2011. Potential of coculture in vitro models to study inflammatory and sensitizing effects of particles on the lung. Toxicol. in vitro 25, 1516-1534.
69. Kovar, J.L., Simpson, M.A., Schutz-Geschwender, A., Olive, D.M., 2007. A systematic approach to the development of fluorescent contrast agents for optical imaging of mouse cancer models. Anal. Biochem. 367, 1-12. (Pubitemid 46938663)
70. Labiris, N.R., Dolovich, M.B., 2003. Pulmonary drug delivery. Part I: Physiological factors affecting therapeutic effectiveness of aerosolized medications. Br. J. Clin. Pharmacol. 56, 588-599. (Pubitemid 37491710)
71. Lee, P.S., Gorski, R.A., Hering, W.E., Chan, T.L., 1987. Lung clearance of inhaled particles after exposure to carbon black generated from a resuspension system. Environ. Res. 43, 364-373.
72. Lehmann, A.D., Daum, N., Bur, M., Lehr, C.M., Gehr, P., Rothen-Rutishauser, B.M., 2011. An in vitro triple cell co-culture model with primary cells mimicking the human alveolar epithelial barrier. Eur. J. Pharm. Biopharm. e.V. 77, 398-406.
73. Liedtke, C.M., 1988. Differentiated properties of rabbit tracheal epithelial cells in primary culture. Am. J. Physiol. 255, C760-C770.
74. Lim, S.H., Park, H.W., Shin, C.H., Kwon, J.H., Kim, C.W., 2009. Human insulin microcrystals with lactose carriers for pulmonary delivery. Biosci. Biotechnol. Biochem. 73, 2576-2582.
75. Linder, A., Friedel, G., Fritz, P., Kivisto, K.T., McClellan, M., Toomes, H., 1996. The exvivo isolated, perfused human lung model: description and potential applications. Thorac. Cardiovasc. Surg. 44, 140-146. (Pubitemid 26246968)
76. Liu, F.Y., Shao, Z., Kildsig, D.O., Mitra, A.K., 1993. Pulmonary delivery of free and liposomal insulin. Pharm. Res. 10, 228-232. (Pubitemid 23041736)
77. Livraghi, A., Randell, S.H., 2007. Cystic fibrosis and other respiratory diseases of impaired mucus clearance. Toxicol. Pathol. 35, 116-129. (Pubitemid 46328419)
78. Lombry, C., Marteleur, A., Arras, M., Lison, D., Louahed, J., Renauld, J.C., Preat, V., Vanbever, R., 2004. Local and systemic immune responses to intratracheal instillation of antigen and DNA vaccines in mice. Pharm. Res. 21, 127-135. (Pubitemid 38122301)
79. Longest, P.W., Hindle, M., 2011. Numerical model to characterize the size increase of combination drug and hygroscopic excipient nanoparticle aerosols. Aerosol. Sci. Technol. 45, 884-899.
80. Longest, P.W., McLeskey Jr., J.T., Hindle, M., 2010. Characterization of nanoaerosol size change during enhanced condensational growth. Aerosol. Sci. Technol. 44, 473-483.
81. Longest, P.W., Tian, G., Li, X., Son, Y.J., Hindle, M., 2012. Performance of combination drug and hygroscopic excipient submicrometer particles from a softmist inhaler in a characteristic model of the airways. Ann. Biomed. Eng. 40, 2596-2610.
82. Macdonald, C., Shao, D., Oli, A., Agu, R.U., 2013. Characterization of Calu-3 cell monolayers as a model of bronchial epithelial transport: organic cation interaction studies. J. Drug Target. 21, 97-106.
83. Mainelis, G., Seshadri, S., Garbuzenko, O.B., Han, T., Wang, Z., Minko, T., 2013. Characterization and application of a nose-only exposure chamber for inhalation delivery of liposomal drugs and nucleic acids to mice. J. Aerosol Med. Pulm. Drug Deliv.
84. Marple, V.A., Roberts, D.L., Romay, F.J., Miller, N.C., Truman, K.G., Van Oort, M., Olsson, B., Holroyd, M.J., Mitchell, J.P., Hochrainer, D., 2003. Next generation pharmaceutical impactor (a new impactor for pharmaceutical inhaler testing). Part I: Design. J. Aerosol Med. 16, 283-299. (Pubitemid 37169639)
85. Martin, J.G., Campbell, H.R., Iijima, H., Gautrin, D., Malo, J.L., Eidelman, D.H., Hamid, Q., Maghni, K., 2003. Chlorine-induced injury to the airways in mice. Am. J. Respir. Crit. Care Med. 168, 568-574. (Pubitemid 37088600)
86. Martin, G.P., MacRitchie, H.B., Marriott, C., Zeng, X.M., 2006. Characterisation of a carrier-free dry powder aerosol formulation using inertial impaction and laser diffraction. Pharm. Res. 23, 2210-2219.
87. Martin, A.R., Thompson, R.B., Finlay, W.H., 2008. MRI measurement of regional lung deposition in mice exposed nose-only to nebulized superparamagnetic iron oxide nanoparticles. J. Aerosol Med. Pulm. Drug Deliv. 21, 335-342.
88. Martonen, T., Isaacs, K., Hwang, D., 2005. Three-dimensional simulations of airways within human lungs. Cell Biochem. Biophys. 42, 223-249. (Pubitemid 41389398)
89. Mehendale, H.M., Angevine, L.S., Ohmiya, Y., 1981. The isolated perfused lung - a critical evaluation. Toxicology 21, 1-36. (Pubitemid 11087330)
90. Messina, M.S., O'Riordan, T.G., Smaldone, G.C., 1991. Changes in mucociliary clearance during acute exacerbations of asthma. Am. Rev. Respir. Dis. 143, 993-997.
91. Mitchell, J.P., Nagel, M.W., 2003a. Cascade impactors for the size characterization of aerosols from medical inhalers: their uses and limitations. J. Aerosol. Med. 16, 341-377. (Pubitemid 38120942)
92. Mitchell, J.P., Nagel, M.W., Doyle, C.C., Ali, R.S., Avvakoumova, V.I., Christopher, J.D., Quiroz, J., Strickland, H., Tougas, T., Lyapustina, S., 2010. Relative precision of inhaler aerodynamic particle size distribution (APSD) metrics by full resolution and abbreviated andersen cascade impactors (ACIs): part 2-investigation of bias in extra-fine mass fraction with AIM-HRT impactor. AAPS PharmSciTech. 11, 1115-1118.
93. Mitchell, J., Bauer, R., Lyapustina, S., Tougas, T., Glaab, V., 2011. Non-impactor-based methods for sizing of aerosols emitted from orally inhaled and nasal drug products (OINDPs). AAPS PharmSciTech. 12, 965-988.
94. Mohammed, H., Roberts, D.L., Copley, M., Hammond, M., Nichols, S.C., Mitchell, J.P., 2012. Effect of sampling volume on dry powder inhaler (DPI)-emitted aerosol aerodynamic particle size distributions (APSDs) measured by the Next-Generation Pharmaceutical Impactor (NGI) and the Andersen eight-stage cascade impactor (ACI). AAPS PharmSciTech. 13, 875-882.
95. Morris, J.B., Wilkie, W.S., Shusterman, D.J., 2005. Acute respiratory responses of the mouse to chlorine. Toxicol. Sci. 83, 380-387. (Pubitemid 40227908)
96. Mosbah, K., Ruiz-Cabello, J., Berthezene, Y., Cremillieux, Y., 2008. Aerosols and gaseous contrast agents for magnetic resonance imaging of the lung. Contrast Media Mol. Imaging 3, 173-190.
97. Nasr, M.M., Ross, D.L., Miller, N.C., 1997. Effect of drug load and plate coating on the particle size distribution of a commercial albuterol metered dose inhaler (MDI) determined using the Andersen and Marple-Miller cascade impactors. Pharm. Res. 14, 1437-1443. (Pubitemid 27481076)
98. Newman, S.P., 1993. Scintigraphic assessment of therapeutic aerosols. Crit. Rev. Ther. Drug Carrier Syst. 10, 65-109. (Pubitemid 23107933)
99. Newman, S.P., Chan, H.K., 2008. In vitro/in vivo comparisons in pulmonary drug delivery. J. Aerosol Med. Pulm. Drug Deliv. 21, 77-84.
100. Newman, S.P., Pitcairn, G.R., Hirst, P.H., 2001. A brief history of gamma scintigraphy. J. Aerosol Med. 14, 139-145. (Pubitemid 32744346)
101. Niven, R.W., 1995. Delivery of biotherapeutics by inhalation aerosol. Crit. Rev. Ther. Drug Carrier Syst. 12, 151-231.
102. Niven, R.W., Rypacek, F., Byron, P.R., 1990. Solute absorption from the airways of the isolated rat lung. III. Absorption of several peptidase-resistant, synthetic polypeptides: poly-(2-hydroxyethyl)-aspartamides. Pharm. Res. 7, 990-994. (Pubitemid 20366724)
103. Noone, P.G., Bennett, W.D., Regnis, J.A., Zeman, K.L., Carson, J.L., King, M., Boucher, R.C., Knowles, M.R., 1999. Effect of aerosolized uridine-50-triphosphate on airway clearance with cough in patients with primary ciliary dyskinesia. Am. J. Respir. Crit. Care. Med. 160, 144-149. (Pubitemid 29326080)
104. Ntziachristos, V., Culver, J.P., Rice, B.W., 2008. Small-animal optical imaging. J. Biomed. Opt. 13, 011001.
105. Oberdorster, G., Cox, C., Gelein, R., 1997. Intratracheal instillation versus intratracheal-inhalation of tracer particles for measuring lung clearance function. Exp. Lung Res. 23, 17-34. (Pubitemid 27065382)
106. O'Callaghan, C., Barry, P.W., 1997. The science of nebulised drug delivery. Thorax 52 (Suppl. 2), S31-S44. (Pubitemid 27239451)
107. Olsson, B., 1995. Aerosol particle generation from dry powder inhalers: can they equal pressurized metered dose inhalers? J. Aerosol Med. 8 (Suppl. 3), S13-S18 (discussion S19).
108. Orton, T.C., Anderson, M.W., Pickett, R.D., Eling, T.E., Fouts, J.R., 1973. Xenobiotic accumulation and metabolism by isolated perfused rabbit lungs. J. Pharmacol. Exp. Ther. 186, 482-497.
109. Pang, Y., Sakagami, M., Byron, P.R., 2005. The pharmacokinetics of pulmonary insulin in the in vitro isolated perfused rat lung: implications of metabolism and regional deposition. Eur. J. Pharm. Sci. 25, 369-378. (Pubitemid 40853864)
110. Pang, Y., Sakagami, M., Byron, P.R., 2007. Insulin self-association: effects on lung disposition kinetics in the airways of the isolated perfused rat lung (IPRL). Pharm. Res. 24, 1636-1644. (Pubitemid 47206614)
111. Park, C.W., Rhee, Y.S., Vogt, F.G., Hayes Jr., D., Zwischenberger, J.B., DeLuca, P.P., Mansour, H.M., 2012. Advances in microscopy and complementary imaging techniques to assess the fate of drugs ex vivo in respiratory drug delivery: an invited paper. Adv. Drug Deliv. Rev. 64, 344-356.
112. Patel, L.N., Wang, J., Kim, K.J., Borok, Z., Crandall, E.D., Shen, W.C., 2009. Conjugation with cationic cell-penetrating peptide increases pulmonary absorption of insulin. Mol. Pharm. 6, 492-503.
113. Patel, B., Gauvin, R., Absar, S., Gupta, V., Gupta, N., Nahar, K., Khademhosseini, A., Ahsan, F., 2012a. Computational and bioengineered lungs as alternatives to whole animal, isolated organ, and cell-based lung models. Am. J. Physiol. Lung Cell. Mol. Physiol. 303, L733-L747.
114. Patel, B., Gupta, V., Ahsan, F., 2012b. PEG-PLGA based large porous particles for pulmonary delivery of a highly soluble drug, low molecular weight heparin. J. Control. Release 162, 310-320.
115. Patra, A.L., Afify, E.M., 1983. An experimental study of velocity distribution in a human lung cast. J. Biomech. Eng. 105, 381-388. (Pubitemid 14165600)
116. Patton, J.S., Fishburn, C.S., Weers, J.G., 2004a. The lungs as a portal of entry for systemic drug delivery. Proc. Am. Thorac. Soc. 1, 338-344.
117. Pauluhn, J., 1994. Validation of an improved nose-only exposure system for rodents. J. Appl. Toxicol. 14, 55-62. (Pubitemid 24044873)
118. Pauluhn, J., 2003. Overview of testing methods used in inhalation toxicity: from facts to artifacts. Toxicol. Lett. 140-141, 183-193. (Pubitemid 36378937)
119. Pauluhn, J., Thiel, A., 2007. A simple approach to validation of directed-flow noseonly inhalation chambers. J. Appl. Toxicol. 27, 160-167. (Pubitemid 46480583)
120. Perring, S., Summers, Q., Fleming, J.S., Nassim, M.A., Holgate, S.T., 1994. A new method of quantification of the pulmonary regional distribution of aerosols using combined CT and SPECT and its application to nedocromil sodium administered by metered dose inhaler. Br. J. Radiol. 67, 46-53. (Pubitemid 24026446)
121. Phelps, M.E., 2000. Positron emission tomography provides molecular imaging of biological processes. Proc. Natl. Acad. Sci. USA 97, 9226-9233. (Pubitemid 30627544)
122. Phipps, P.R., Gonda, I., Anderson, S.D., Bailey, D., Bautovich, G., 1994. Regional deposition of saline aerosols of different tonicities in normal and asthmatic subjects. Eur. Respir. J. 7, 1474-1482. (Pubitemid 24268335)
123. Piacentini, E., Lopez-Aguilar, J., Garcia-Martin, C., Villagra, A., Saenz-Valiente, A., Murias, G., Fernandez-Segoviano, P., Hotchkiss, J.R., Blanch, L., 2008. Effects of vascular flow and PEEP in a multiple hit model of lung injury in isolated perfused rabbit lungs. J. Trauma. 65, 147-153.
124. Piwnica-Worms, D., Schuster, D.P., Garbow, J.R., 2004. Molecular imaging of hostpathogen interactions in intact small animals. Cell Microbiol. 6, 319-331. (Pubitemid 38379815)
125. Port, J.L., Yamaguchi, K., Du, B., De Lorenzo, M., Chang, M., Heerdt, P.M., Kopelovich, L., Marcus, C.B., Altorki, N.K., Subbaramaiah, K., Dannenberg, A.J., 2004. Tobacco smoke induces CYP1B1 in the aerodigestive tract. Carcinogenesis 25, 2275-2281. (Pubitemid 39534867)
126. Qi, Y., Zhao, G., Liu, D., Shriver, Z., Sundaram, M., Sengupta, S., Venkataraman, G., Langer, R., Sasisekharan, R., 2004. Delivery of therapeutic levels of heparin and low-molecular-weight heparin through a pulmonary route. Proc. Natl. Acad. Sci. USA 101, 9867-9872. (Pubitemid 38869328)
127. Ramalingam, S., Belani, C.P., 2007. Recent advances in targeted therapy for nonsmall cell lung cancer. Expert Opin. Ther. Targets 11, 245-257. (Pubitemid 46188817)
128. Rao, G.N., Banick, D.W., Pacenti, D.M., 1997. Particle size distribution of a suspension aerosol using Andersen and Marple-Miller cascade impactors. Pharm. Res. 14, 1272-1274. (Pubitemid 27432556)
129. Rasmussen, R.E., Bhalla, D.K., 1989. Transport across rat trachea in vitro after exposure to cytoskeleton-active drugs in vitro or to ozone in vivo. Exp. Lung Res. 15, 253-268. (Pubitemid 19097745)
130. Richard, J.C., Zhou, Z., Chen, D.L., Mintun, M.A., Piwnica-Worms, D., Factor, P., Ponde, D.E., Schuster, D.P., 2004. Quantitation of pulmonary transgene expression with PET imaging. J. Nucl. Med. 45, 644-654. (Pubitemid 47618596)
131. Rothen-Rutishauser, B.M., Kiama, S.G., Gehr, P., 2005. A three-dimensional cellular model of the human respiratory tract to study the interaction with particles. Am. J. Respir. Cell Mol. Biol. 32, 281-289. (Pubitemid 40478303)
132. Saha, G.B., MacIntyre, W.J., Go, R.T., 1992. Cyclotrons and positron emission tomography radiopharmaceuticals for clinical imaging. Semin. Nucl. Med. 22, 150-161.
133. Sakagami, M., 2006. In vivo, in vitro and ex vivo models to assess pulmonary absorption and disposition of inhaled therapeutics for systemic delivery. Adv. Drug Deliv. Rev. 58, 1030-1060. (Pubitemid 44712023)
134. Salomon, J.J., Endter, S., Tachon, G., Falson, F., Buckley, S.T., Ehrhardt, C., 2012. Transport of the fluorescent organic cation 4-(4-(dimethylamino)styryl)-Nmethylpyridinium iodide (ASP+) in human respiratory epithelial cells. European Journal of Pharmaceutics and Biopharmaceutics: Official Journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.81, 351-359.
135. Schanker, L.S., 1978. Drug absorption from the lung. Biochem. Pharmacol. 27, 381-385. (Pubitemid 8276840)
136. Sebti, T., Amighi, K., 2006. Preparation and in vitro evaluation of lipidic carriers and fillers for inhalation. Eur. J. Pharm. Biopharm. 63, 51-58.
137. Selg, E., Acevedo, F., Nybom, R., Blomgren, B., Ryrfeldt, A., Gerde, P., 2010. Delivering horseradish peroxidase as a respirable powder to the isolated, perfused, and ventilated lung of the rat: the pulmonary disposition of an inhaled model biopharmaceutical. J. Aerosol Med. Pulm. Drug Deliv. 23, 273-284.
138. Selg, E., Ewing, P., Acevedo, F., Sjoberg, C.O., Ryrfeldt, A., Gerde, P., 2012. Dry powder inhalation exposures of the endotracheally intubated rat lung, ex vivo and in vivo: the pulmonary pharmacokinetics of fluticasone furoate. J. Aerosol Med. Pulm. Drug Deliv.
139. Shekunov, B.Y., Chattopadhyay, P., Tong, H.H., Chow, A.H., 2007. Particle size analysis in pharmaceutics: principles, methods and applications. Pharm. Res. 24, 203-227. (Pubitemid 46072181)
140. Shi, S., Ashley, E.S., Alexander, B.D., Hickey, A.J., 2009. Initial characterization of micafungin pulmonary delivery via two different nebulizers and multivariate data analysis of aerosol mass distribution profiles. AAPS PharmSciTech. 10, 129-137.
141. Siekmeier, R., Scheuch, G., 2008. Systemic treatment by inhalation of macromolecules-principles, problems, and examples. J. Physiol. Pharmacol. 59 (Suppl. 6), 53-79.
142. Siekmeier, R., Scheuch, G., 2009. Treatment of systemic diseases by inhalation of biomolecule aerosols. J. Physiol. Pharmacol. 60 (Suppl. 5), 15-26.
143. Snell, N.J., Ganderton, D., 1999. Assessing lung deposition of inhaled medications. Consensus statement from a workshop of the British Association for Lung Research, held at the Institute of Biology, London, UK on 17 April 1998. Respir. Med. 93, 123-133. (Pubitemid 29062720)
144. Sobande, P.O., Kercsmar, C.M., 2008. Inhaled corticosteroids in asthma management. Respir. Care. 53, 625-633.
145. Sood, B.G., Shen, Y., Latif, Z., Chen, X., Sharp, J., Neelavalli, J., Joshi, A., Slovis, T.L., Haacke, E.M., 2008. Aerosol delivery in ventilated newborn pigs: an MRI evaluation. Pediatr. Res. 64, 159-164.
146. Sood, B.G., Shen, Y., Latif, Z., Galli, B., Dawe, E.J., Haacke, E.M., 2010. Effective aerosol delivery during high-frequency ventilation in neonatal pigs. Respirology 15, 551-555.
147. Stahlhofen, W., Koebrich, R., Rudolf, G., Scheuch, G., 1990. Short-term and long-term clearance of particles from the upper human respiratory tract as function of particle size. J. Aerosol Med. 21, S407-S410.
148. Stavert, D.M., Lehnert, B.E., 1990. Nitric oxide and nitrogen oxide as inducers of acute pulmonary injury when inhaled at relatively high concentrations for brief periods. Inhal. Toxicol. 2, 53-67.
149. Steimer, A., Haltner, E., Lehr, C.M., 2005. Cell culture models of the respiratory tract relevant to pulmonary drug delivery. J. Aerosol Med. 18, 137-182. (Pubitemid 40911357)
150. Suarez, S., Garcia-Contreras, L., Sarubbi, D., Flanders, E., O'Toole, D., Smart, J., Hickey, A.J., 2001. Facilitation of pulmonary insulin absorption by H-MAP: pharmacokinetics and pharmacodynamics in rats. Pharm. Res. 18, 1677-1684. (Pubitemid 34020422)
151. Sung, J.C., Garcia-Contreras, L., Verberkmoes, J.L., Peloquin, C.A., Elbert, K.J., Hickey, A.J., Edwards, D.A., 2009a. Dry powder nitroimidazopyran antibiotic PA-824 aerosol for inhalation. Antimicrob. Agents Chemother. 53, 1338-1343.
152. Sung, J.C., Padilla, D.J., Garcia-Contreras, L., Verberkmoes, J.L., Durbin, D., Peloquin, C.A., Elbert, K.J., Hickey, A.J., Edwards, D.A., 2009b. Formulation and pharmacokinetics of self-assembled rifampicin nanoparticle systems for pulmonary delivery. Pharm. Res. 26, 1847-1855.
153. Taki, M., Marriott, C., Zeng, X.M., Martin, G.P., 2010. Aerodynamic deposition of combination dry powder inhaler formulations in vitro: a comparison of three impactors. Int. J. Pharm. 388, 40-51.
154. Taratula, O., Dmochowski, I.J., 2010. Functionalized 129Xe contrast agents for magnetic resonance imaging. Curr. Opin. Chem. Biol. 14, 97-104.
155. Thomas, C., Rawat, A., Bai, S., Ahsan, F., 2008. Feasibility study of inhaled hepatitis B vaccine formulated with tetradecylmaltoside. J. Pharm. Sci. 97, 1213-1223.
156. Thompson, R.B., Finlay, W.H., 2012. Using MRI to measure aerosol deposition. J. Aerosol Med. Pulm. Drug Deliv. 25, 55-62.
157. Tian, X., Tao, H., Brisolara, J., Chen, J., Rando, R.J., Hoyle, G.W., 2008. Acute lung injury induced by chlorine inhalation in C57BL/6 and FVB/N mice. Inhal. Toxicol. 20, 783-793. (Pubitemid 352032210)
158. Tronde, A., Norden, B., Marchner, H., Wendel, A.K., Lennernas, H., Bengtsson, U.H., 2003. Pulmonary absorption rate and bioavailability of drugs in vivo in rats: structure-absorption relationships and physicochemical profiling of inhaled drugs. J. Pharm. Sci. 92, 1216-1233. (Pubitemid 36676468)
159. Villenave, R., Thavagnanam, S., Sarlang, S., Parker, J., Douglas, I., Skibinski, G., Heaney, L.G., McKaigue, J.P., Coyle, P.V., Shields, M.D., Power, U.F., 2012. In vitro modeling of respiratory syncytial virus infection of pediatric bronchial epithelium, the primary target of infection in vivo. Proc. Natl. Acad. Sci. USA 109, 5040-5045.
160. Vincent, R., Bjarnason, S.G., Adamson, I.Y., Hedgecock, C., Kumarathasan, P., Guenette, J., Potvin, M., Goegan, P., Bouthillier, L., 1997. Acute pulmonary toxicity of urban particulate matter and ozone. Am. J. Pathol. 151, 1563-1570. (Pubitemid 27527919)
161. Weda, M., Zanen, P., de Boer, A.H., Barends, D.M., Frijlink, H.W., 2004. An investigation into the predictive value of cascade impactor results for side effects of inhaled salbutamol. Int. J. Pharm. 287, 79-87. (Pubitemid 39487246)
162. Wong, B.A., 2007. Inhalation exposure systems: design, methods and operation. Toxicol. Pathol. 35, 3-14. (Pubitemid 46328404)
163. Wong, W., Crapper, J., Chan, H.K., Traini, D., Young, P.M., 2010. Pharmacopeial methodologies for determining aerodynamic mass distributions of ultra-high dose inhaler medicines. J. Pharm. Biomed. Anal. 51, 853-857.
164. Wu, R., Martin, W.R., Robinson, C.B., St George, J.A., Plopper, C.G., Kurland, G., Last, J.A., Cross, C.E., McDonald, R.J., Boucher, R., 1990. Expression of mucin synthesis and secretion in human tracheobronchial epithelial cells grown in culture. Am. J. Respir. Cell Mol. Biol. 3, 467-478.
165. Xie, Y., Aillon, K.L., Cai, S., Christian, J.M., Davies, N.M., Berkland, C.J., Forrest, M.L., 2010. Pulmonary delivery of cisplatin-hyaluronan conjugates via endotracheal instillation for the treatment of lung cancer. Int. J. Pharm. 392, 156-163.
166. Yamada, Y., Koizumi, A., Inaba, J., 1998. A new method of casting human respiratory tract for aerosol deposition studies. Radiat. Prot. Dosimetry 79, 269-272. (Pubitemid 28466945)
167. Yang, T., Mustafa, F., Bai, S., Ahsan, F., 2004. Pulmonary delivery of low molecular weight heparins. Pharm. Res. 21, 2009-2016. (Pubitemid 40941220)
168. Yang, T., Hussain, A., Bai, S., Khalil, I.A., Harashima, H., Ahsan, F., 2006. Positively charged polyethylenimines enhance nasal absorption of the negatively charged drug, low molecular weight heparin. J. Control. Release 115, 289-297. (Pubitemid 44634847)
169. Yang, X., Liu, Y., Liu, C., Zhang, N., 2012. Biodegradable solid lipid nanoparticle flocculates for pulmonary delivery of insulin. J. Biomed. Nanotechnol. 8, 834-842.
170. Yeh, H.C., Schum, G.M., Duggan, M.T., 1979. Anatomic models of the tracheobronchial and pulmonary regions of the rat. Anat. Rec. 195, 483-492. (Pubitemid 10210902)
171. Yi, D., Price, A., Panoskaltsis-Mortari, A., Naqwi, A., Wiedmann, T.S., 2010. Measurement of the distribution of aerosols among mouse lobes by fluorescent imaging. Anal. Biochem. 403, 88-93.
172. Yi, D., Wiedmann, T.S., Naqwi, A., Price, A.P., Panoskaltsis-Mortari, A., 2012. Distribution of aerosols in murine obliterative bronchiolitis lungs by fluorescent imaging. Exp. Lung Res. 38, 325-332.
173. Yoo, N.Y., Youn, Y.S., Oh, N.M., Oh, K.T., Lee, D.K., Cha, K.H., Oh, Y.T., Lee, E.S., 2011. Antioxidant encapsulated porous poly(lactide-co- glycolide) microparticles for developing long acting inhalation system. Colloids Surf. B. Biointerfaces 88, 419-424.
174. Yu, J., Chien, Y.W., 1997. Pulmonary drug delivery: physiologic and mechanistic aspects. Crit. Rev. Ther. Drug Carrier Syst. 14, 395-453. (Pubitemid 28036074)
175. Zhao, Y.Z., Li, X., Lu, C.T., Xu, Y.Y., Lv, H.F., Dai, D.D., Zhang, L., Sun, C.Z., Yang, W., Li, X.K., Zhao, Y.P., Fu, H.X., Cai, L., Lin, M., Chen, L.J., Zhang, M., 2012. Experiment on the feasibility of using modified gelatin nanoparticles as insulin pulmonary administration system for diabetes therapy. Acta Diabetol. 49, 315-325.