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Current Drug Delivery

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ISSN (Print): 1567-2018
ISSN (Online): 1875-5704

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Review Article

Fundamentals and Applications of Isolated Perfused Lung (IPL) Model in the Development of Pulmonary Drug Delivery

Author(s): Katayoon Mireskandari, Yalda H. Ardakani, Ebrahim S. Moghadam, Farzaneh Ketabchi and Mohammadreza Rouini*

Volume 20, Issue 10, 2023

Published on: 26 September, 2022

Page: [1425 - 1440] Pages: 16

DOI: 10.2174/1567201819666220823161318

Price: $65

Abstract

Estimating parameters such as pulmonary drug disposition and deposited dose, as well as determining the influence of pulmonary pharmacokinetics (PK) on drug efficacy and safety, are critical factors for the development of inhaled drug products and help to achieve a better understanding of the drugs’ fate in the lungs. Pulmonary disposition and PK have remained poorly understood due to the difficulty to access pulmonary fluids, compared to other biological fluids, such as plasma, for direct or surrogate measurement of the concentration of the active compounds and their metabolites in the lung. The use of the isolated perfused lung model (IPL) has become more common, and it is considered a useful tool to increase understanding in this area since it offers the possibility of controlling the administration and easier sampling of perfusate and lavage fluid. The model also provides an opportunity to study the relationship between PK and pharmacodynamics. This review describes the fundamentals of the IPL model, such as preparation and setting up the method, species selection, drug administration, and lung viability investigation. Besides, different applications of the IPL model like pharmacodynamic studies, pharmacokinetic parameters studies such as absorption, distribution, and metabolism, and evaluation of inhaled formulation have also been reviewed.

Keywords: Pulmonary drug delivery, pulmonary drug disposition, inhaled formulations, isolated perfused lung model, pulmonary pharmacokinetics, IPL model.

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[1]
Jones, R.M.; Harrison, A. A new methodology for predicting human pharmacokinetics for inhaled drugs from oratracheal pharmacokinetic data in rats. Xenobiotica, 2012, 42(1), 75-85.
[http://dx.doi.org/10.3109/00498254.2011.626465] [PMID: 22077102]
[2]
Zhong, H.; Chan, G.; Hu, Y.; Hu, H.; Ouyang, D. A comprehensive map of FDA-approved pharmaceutical products. Pharmaceutics, 2018, 10(4), 263.
[http://dx.doi.org/10.3390/pharmaceutics10040263] [PMID: 30563197]
[3]
Tronde, A.; Bosquillon, C.; Forbes, B. The isolated perfused lung for drug absorption studies. In: Drug Absorption Studies; , 2008; pp. 135-163.
[4]
Evans, C.L.; Hsu, F.Y.; Kosaka, T. Utilization of blood sugar and formation of lactic acid by the lungs. J. Physiol., 1934, 82(1), 41-61.
[http://dx.doi.org/10.1113/jphysiol.1934.sp003158] [PMID: 16994566]
[5]
Niemeier, R.W. The isolated perfused lung. Environ. Health Perspect., 1984, 56, 35-41.
[http://dx.doi.org/10.1289/ehp.845635] [PMID: 6383800]
[6]
Pacheco-Baltazar, A.; Arreola-Ramírez, J.L.; Alquicira-Mireles, J.; Segura-Medina, P. Isolated lung perfusion system in the rabbit model. J. Vis. Exp., 2021, 173.
[7]
Sakagami, M. In vivo, in vitro and ex vivo models to assess pulmonary absorption and disposition of inhaled therapeutics for systemic delivery. Adv. Drug Deliv. Rev., 2006, 58(9-10), 1030-1060.
[http://dx.doi.org/10.1016/j.addr.2006.07.012] [PMID: 17010473]
[8]
Tronde, A.; Nordén, B.; Jeppsson, A.B.; Brunmark, P.; Nilsson, E.; Lennernäs, H.; Bengtsson, U.H. Drug absorption from the isolated perfused rat lung-correlations with drug physicochemical properties and epithelial permeability. J. Drug Target., 2003, 11(1), 61-74.
[http://dx.doi.org/10.1080/1061186031000086117] [PMID: 12852442]
[9]
Fröhlich, E.; Salar-Behzadi, S. Toxicological assessment of inhaled nanoparticles: Role of in vivo, ex vivo, in vitro, and in silico studies. Int. J. Mol. Sci., 2014, 15(3), 4795-4822.
[http://dx.doi.org/10.3390/ijms15034795] [PMID: 24646916]
[10]
Slama, A.; Raber, C.; Hedderich, C.; Stockhammer, P.; Hegedüs, B.; Koch, A.; Theegarten, D.; Ploenes, T.; Aigner, C. Implementation of an experimental isolated lung perfusion model on surgically resected human lobes. Sci. Rep., 2019, 9(1), 12193.
[http://dx.doi.org/10.1038/s41598-019-48719-8] [PMID: 31434960]
[11]
Madlova, M.; Bosquillon, C.; Asker, D.; Dolezal, P.; Forbes, B. In-vitro respiratory drug absorption models possess nominal functional P-glycoprotein activity. J. Pharm. Pharmacol., 2010, 61(3), 293-301.
[http://dx.doi.org/10.1211/jpp.61.03.0003] [PMID: 19222901]
[12]
Corrin, B. Metabolic activities of the lung. J. Clin. Pathol., 1981, 34(5), 573-573.
[http://dx.doi.org/10.1136/jcp.34.5.573-a]
[13]
Dinis-Oliveira, R.J.; Valle, M.J.D.J.; Bastos, M.L.; Carvalho, F.; Sánchez Navarro, A. Kinetics of paraquat in the isolated rat lung: Influence of sodium depletion. Xenobiotica, 2006, 36(8), 724-737.
[http://dx.doi.org/10.1080/00498250600790331] [PMID: 16891252]
[14]
Leary, W.P.; Smith, U. In situ perfusion of isolated rat lung. Life Sci., 1970, 9(23), 1321-1326.
[http://dx.doi.org/10.1016/0024-3205(70)90039-1] [PMID: 4321771]
[15]
Liu, X.; Wang, J.Y.; Khlentzos, A.M.; Fontaine, F.; Nikolovski, J.; Goh, L.A.; Roberts, M.S. Influence of perfusate composition on drug disposition in the in-situ perfused rat lung. Int. J. Pharm., 2009, 382(1-2), 192-197.
[http://dx.doi.org/10.1016/j.ijpharm.2009.08.028] [PMID: 19716867]
[16]
Herget, J.; Chovanec, M. Isolated perfused murine lung. Drug Discov. Today Dis. Models, 2010, 7(3-4), 131-135.
[http://dx.doi.org/10.1016/j.ddmod.2011.03.008]
[17]
Tronde, A.; Krondahl, E.; von Euler-Chelpin, H.; Brunmark, P.; Hultkvist Bengtsson, U.; Ekström, G.; Lennernäs, H. High airway-to-blood transport of an opioid tetrapeptide in the isolated rat lung after aerosol delivery. Peptides, 2002, 23(3), 469-478.
[http://dx.doi.org/10.1016/S0196-9781(01)00624-6] [PMID: 11835996]
[18]
Uhlig, S.; Wollin, L. An improved setup for the isolated perfused rat lung. J. Pharmacol. Toxicol. Methods, 1994, 31(2), 85-94.
[http://dx.doi.org/10.1016/1056-8719(94)90047-7] [PMID: 8032099]
[19]
Rhoades, R.A.; Shaw, M.E.; Eskew, M.L. Influence of altered O2 tension on substrate metabolism in perfused rat lung. Am. J. Physiol., 1975, 229(6), 1476-1479.
[http://dx.doi.org/10.1152/ajplegacy.1975.229.6.1476] [PMID: 1211480]
[20]
Stubbs, W.A.; Kelly, D.M.; Walters, F.J.; Alberti, K.G.M.M. The metabolic characteristics of the ventilated and non-ventilated perfused rat lung. Biochem. Soc. Trans., 1977, 5(5), 1312-1314.
[http://dx.doi.org/10.1042/bst0051312] [PMID: 21820]
[21]
Roth, R.A.; Gillis, C.N. Effect of ventilation on removal of [14C]mescaline by perfused rabbit lung. Biochem. Pharmacol., 1977, 26(15), 1446-1448.
[http://dx.doi.org/10.1016/0006-2952(77)90373-2] [PMID: 901559]
[22]
Mehendale, H.M. Use of isolated perfused lung in determining pulmonary disposition and potential toxicological significance of inhaled environmental pollutants. Environ. Toxicol. Chem., 1982, 1(3), 231-244.
[http://dx.doi.org/10.1002/etc.5620010306]
[23]
Biancosino, C.; Albert, M.; Linder, A. Acute toxicity of irinotecan in the ex vivo isolated perfused human lung model high-dose therapy during isolated perfusion without acute toxic lung edema. Interact. Cardiovasc. Thorac. Surg., 2007, 6(5), 583-587.
[http://dx.doi.org/10.1510/icvts.2007.152165] [PMID: 17670737]
[24]
Linder, A.; Friedel, G.; Fritz, P.; Kivistö, K.; McClellan, M.; Toomes, H. The ex vivo isolated, perfused human lung model: Description and potential applications. Thorac. Cardiovasc. Surg., 1996, 44(3), 140-146.
[http://dx.doi.org/10.1055/s-2007-1012003] [PMID: 8858797]
[25]
Watkins, C.A.; Rannels, D.E. In situ perfusion of rat lungs: Stability and effects of oxygen tension. J. Appl. Physiol., 1979, 47(2), 325-329.
[http://dx.doi.org/10.1152/jappl.1979.47.2.325] [PMID: 468688]
[26]
Dehler, M.; Zessin, E.; Bärtsch, P.; Mairbäurl, H. Hypoxia causes permeability oedema in the constant-pressure perfused rat lung. Eur. Respir. J., 2006, 27(3), 600-606.
[http://dx.doi.org/10.1183/09031936.06.00061505] [PMID: 16507862]
[27]
Creamer, K.M. McCLOUD, L.L.; Fisher, L.; Ehrhart, I.C. Ventilation above closing volume reduces pulmonary vascular resistance hysteresis. Am. J. Respir. Crit. Care Med., 1998, 158(4), 1114-1119.
[http://dx.doi.org/10.1164/ajrccm.158.4.9711081] [PMID: 9769269]
[28]
Peták, F.; Albu, G.; Lele, E.; Hantos, Z.; Morel, D.R.; Fontao, F.; Habre, W. Lung mechanical and vascular changes during positive- and negative-pressure lung inflations: Importance of reference pressures in the pulmonary vasculature. J. Appl. Physiol., 2009, 106(3), 935-942.
[http://dx.doi.org/10.1152/japplphysiol.00831.2007] [PMID: 19112162]
[29]
Albu, G.; Habre, W.; Fontao, F.; Morel, D.R.; Petak, F. The contribution of the pulmonary microvascular pressure in the maintenance of an open lung during mechanical ventilation. Respir. Physiol. Neurobiol., 2007, 157(2-3), 262-269.
[http://dx.doi.org/10.1016/j.resp.2006.12.004] [PMID: 17222590]
[30]
Peták, F.; Habre, W.; Hantos, Z.; Sly, P.D.; Morel, D.R. Effects of pulmonary vascular pressures and flow on airway and parenchymal mechanics in isolated rat lungs. J. Appl. Physiol., 2002, 92(1), 169-178.
[http://dx.doi.org/10.1152/jappl.2002.92.1.169] [PMID: 11744657]
[31]
Lal, H.; Woodward, B.; Williams, K.I. Actions of endothelins and sarafotoxin 6c in the rat isolated perfused lung. Br. J. Pharmacol., 1995, 115(4), 653-659.
[http://dx.doi.org/10.1111/j.1476-5381.1995.tb14982.x] [PMID: 7582486]
[32]
Sundström, E.; Låstbom, L.; Ryrfeldt, Å.; Dahlén, S.E. Interactions among three classes of mediators explain antigen-induced bronchoconstriction in the isolated perfused and ventilated guinea pig lung. J. Pharmacol. Exp. Ther., 2003, 307(1), 408-418.
[http://dx.doi.org/10.1124/jpet.103.053546] [PMID: 12954791]
[33]
Watson, K. E.; Segal, G. S.; Conhaim, R. L. Negative pressure ventilation enhances acinar perfusion in isolated rat lungs. Pulm.Circ., 2018, 8(1), 0-9.
[http://dx.doi.org/10.1177/2045893217753596]
[34]
Muscedere, J.G.; Mullen, J.B.; Gan, K.; Slutsky, A.S. Tidal ventilation at low airway pressures can augment lung injury. Am. J. Respir. Crit. Care Med., 1994, 149(5), 1327-1334.
[http://dx.doi.org/10.1164/ajrccm.149.5.8173774] [PMID: 8173774]
[35]
Uhlig, S.; Heiny, O. Measuring the weight of the isolated perfused rat lung during negative pressure ventilation. J. Pharmacol. Toxicol. Methods, 1995, 33(3), 147-152.
[http://dx.doi.org/10.1016/1056-8719(94)00069-G] [PMID: 7640394]
[36]
Barr, H.A.; Nicholas, T.E.; Power, J.H.T. Control of alveolar surfactant in rats at rest and during prolonged hyperpnoea: Pharmacological evidence for two tissue pools of surfactant. Br. J. Pharmacol., 1988, 93(3), 473-482.
[http://dx.doi.org/10.1111/j.1476-5381.1988.tb10301.x] [PMID: 3370384]
[37]
Veldhuizen, R.A.W.; Tremblay, L.N.; Govindarajan, A.; van Rozendaal, B.A.W.M.; Haagsman, H.P.; Slutsky, A.S. Pulmonary surfactant is altered during mechanical ventilation of isolated rat lung. Crit. Care Med., 2000, 28(7), 2545-2551.
[http://dx.doi.org/10.1097/00003246-200007000-00059] [PMID: 10921592]
[38]
Santos Martínez Martínez, M.; Colino Gandarillas, C.I.; Lanao, J.M.; Sánchez Navarro, A. Influence of flow rate on the disposition of levofloxacin and netilmicin in the isolated rat lung. Eur. J. Pharm. Sci., 2005, 24(4), 325-332.
[http://dx.doi.org/10.1016/j.ejps.2004.11.008] [PMID: 15734299]
[39]
Sharma, A.K.; Linden, J.; Kron, I.L.; Laubach, V.E. Protection from pulmonary ischemia-reperfusion injury by adenosine A2A receptor activation. Respir. Res., 2009, 10(1), 58.
[http://dx.doi.org/10.1186/1465-9921-10-58] [PMID: 19558673]
[40]
Czartolomna, J.; Voelkel, N.F.; Chang, S.W. Permeability characteristics of isolated perfused rat lungs. J. Appl. Physiol., 1991, 70(4), 1854-1860.
[http://dx.doi.org/10.1152/jappl.1991.70.4.1854] [PMID: 2055864]
[41]
Blase, B.; Loomis, T.A. The uptake and metabolism of carbaryl by isolated perfused rabbit lung. Toxicol. Appl. Pharmacol., 1976, 37(3), 481-490.
[http://dx.doi.org/10.1016/0041-008X(76)90210-6] [PMID: 823669]
[42]
Taylor, A.E. Methods in Pulmonary Research; Springer Science & Business Media, 1998, pp. 1-28.
[43]
Wiersma, D.A.; Braselton, W.E.; Roth, R.A. The influence of flow on the metabolism of perfused benzo[a]pyrene by isolated rat lung. Chem. Biol. Interact., 1983, 43(1), 1-15.
[http://dx.doi.org/10.1016/0009-2797(83)90101-1] [PMID: 6295648]
[44]
Ryrfeldt, Å.; Persson, G.; Nilsson, E. Pulmonary disposition of the potent glucocorticoid budesonide, evaluated in an isolated perfused rat lung model. Biochem. Pharmacol., 1989, 38(1), 17-22.
[http://dx.doi.org/10.1016/0006-2952(89)90143-3] [PMID: 2910298]
[45]
Eriksson, J.; Sjögren, E.; Thörn, H.; Rubin, K.; Bäckman, P.; Lennernäs, H. Pulmonary absorption - estimation of effective pulmonary permeability and tissue retention of ten drugs using an ex vivo rat model and computational analysis. Eur. J. Pharm. Biopharm., 2018, 124, 1-12.
[http://dx.doi.org/10.1016/j.ejpb.2017.11.013] [PMID: 29191716]
[46]
Cantor, J.O. CRC Handbook of Animal Models of Pulmonary Disease; Taylor & Francis Group: Milton Park, Oxfordshire, UK, 2018.
[47]
Van Putte, B.P.; Hendriks, J.M.H.; Romijn, S.; Guetens, G.; De Boeck, G.; De Bruijn, E.A.; Van Schil, P.E.Y. Single-pass isolated lung perfusion versus recirculating isolated lung perfusion with melphalan in a rat model. Ann. Thorac. Surg., 2002, 74(3), 893-898.
[http://dx.doi.org/10.1016/S0003-4975(02)03802-X] [PMID: 12238857]
[48]
Ewing, P. A Novel Technology for Studying the Disposition of Drugs and Toxicants in the Lung; Short Inhalation Exposures of the Isolated and Perfused Rat Lung to Respirable Dry Particle Aerosols; Karolinska Institutet: Sweden, 2008.
[49]
Selg, E.; Ewing, P.; Acevedo, F.; Sjöberg, C.O.; Ryrfeldt, Å.; Gerde, P. 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., 2013, 26(4), 181-189.
[http://dx.doi.org/10.1089/jamp.2012.0971] [PMID: 23094685]
[50]
Wang, H.Y.; Port, J.L.; Hochwald, S.N.; Burt, M.E. Revised technique of isolated lung perfusion in the rat. Ann. Thorac. Surg., 1995, 60(1), 211-212.
[http://dx.doi.org/10.1016/S0003-4975(95)00390-8] [PMID: 7598602]
[51]
Otto, T.J.; Trenkner, M.; Stopczyk, A.; Gawdziński, M.; Chelstowska, B. Perfusion and ventilation of isolated canine lungs. Thorax, 1968, 23(6), 645-651.
[http://dx.doi.org/10.1136/thx.23.6.645] [PMID: 4886091]
[52]
Dunbar, J.R.; DeLucia, A.J.; Bryant, L.R. Glutathione status of isolated rabbit lungs. Biochem. Pharmacol., 1984, 33(8), 1343-1348.
[http://dx.doi.org/10.1016/0006-2952(84)90190-4] [PMID: 6712739]
[53]
Ewing, P.; Blomgren, B.; Ryrfeldt, Å.; Gerde, P. 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., 2006, 91(2), 332-340.
[http://dx.doi.org/10.1093/toxsci/kfj104] [PMID: 16415328]
[54]
Srinivasan, H.B.; Vogel, S.M.; Vidyasagar, D.; Malik, A.B. Protective effect of lung inflation in reperfusion-induced lung microvascular injury. Am. J. Physiol. Heart Circ. Physiol., 2000, 278(3), H951-H957.
[http://dx.doi.org/10.1152/ajpheart.2000.278.3.H951] [PMID: 10710364]
[55]
Chang, R.S.; Wright, K.; Effros, R.M. Role of albumin in prevention of edema in perfused rabbit lungs. J. Appl. Physiol., 1981, 50(5), 1065-1070.
[http://dx.doi.org/10.1152/jappl.1981.50.5.1065] [PMID: 7228756]
[56]
Chang, S.W.; Westcott, J.Y.; Henson, J.E.; Voelkel, N.F. Pulmonary vascular injury by polycations in perfused rat lungs. J. Appl. Physiol., 1987, 62(5), 1932-1943.
[http://dx.doi.org/10.1152/jappl.1987.62.5.1932] [PMID: 2885303]
[57]
Smith, B.R.; Bend, J.R. Lung perfusion techniques for xenobiotic metabolism and toxicity studies. Methods Enzymol., 1981, 77, 105-120.
[http://dx.doi.org/10.1016/S0076-6879(81)77015-0] [PMID: 7329294]
[58]
Herget, J.; McMurtry, I.F. Dexamethasone potentiates hypoxic vasoconstriction in salt solution-perfused rat lungs. Am. J. Physiol., 1987, 253(3 Pt 2), H574-H581.
[PMID: 3631295]
[59]
McMurtry, I.F. Angiotensin is not required for hypoxic constriction in salt solution-perfused rat lungs. J. Appl. Physiol., 1984, 56(2), 375-380.
[http://dx.doi.org/10.1152/jappl.1984.56.2.375] [PMID: 6561197]
[60]
Beck-Broichsitter, M.; Schmehl, T.; Seeger, W.; Gessler, T. Evaluating the controlled release properties of inhaled nanoparticles using isolated, perfused, and ventilated lung models. J. Nanomater., 2011, 2011, 1-16.
[http://dx.doi.org/10.1155/2011/163791]
[61]
Seeger, W.; Walmrath, D.; Grimminger, F.; Rosseau, S.; Schütte, H.; Krämer, H.J.; Ermert, L.; Kiss, L. Adult respiratory distress syndrome: Model systems using isolated perfused rabbit lungs. Methods Enzymol., 1994, 233, 549-584.
[http://dx.doi.org/10.1016/S0076-6879(94)33060-3] [PMID: 8015490]
[62]
Sakagami, M.; Byron, P.R.; Rypacek, F. Biochemical evidence for transcytotic absorption of polyaspartamide from the rat lung: Effects of temperature and metabolic inhibitors. J. Pharm. Sci., 2002, 91(9), 1958-1968.
[http://dx.doi.org/10.1002/jps.10188] [PMID: 12210043]
[63]
Byron, P.R.; Niven, R.W. A novel dosing method for drug administration to the airways of the isolated perfused rat lung. J. Pharm. Sci., 1988, 77(8), 693-695.
[http://dx.doi.org/10.1002/jps.2600770810] [PMID: 3210159]
[64]
Sanchez, P.G.; Bittle, G.J.; Burdorf, L.; Pierson, R.N., III; Griffith, B.P. State of Art: Clinical ex vivo lung perfusion: Rationale, current status, and future directions. J. Heart Lung Transplant., 2012, 31(4), 339-348.
[http://dx.doi.org/10.1016/j.healun.2012.01.866] [PMID: 22423980]
[65]
Saldías, F.J.; Comellas, A.; Guerrero, C.; Ridge, K.M.; Rutschman, D.H.; Sznajder, J.I. Time course of active and passive liquid and solute movement in the isolated perfused rat lung model. J. Appl. Physiol., 1998, 85(4), 1572-1577.
[http://dx.doi.org/10.1152/jappl.1998.85.4.1572] [PMID: 9760355]
[66]
Rhoades, R.A. Isolated perfused lung preparation for studying altered gaseous environments. Environ. Health Perspect., 1984, 56, 43-50.
[http://dx.doi.org/10.1289/ehp.845643] [PMID: 6383801]
[67]
O’Neil, J.J. Rat lung metabolism: Glucose utilization by tissue slices and the isolated perfused lung. Thesis, Univ. California, 1974, 867-873.
[68]
Cidem, A.; Bradbury, P.; Traini, D.; Ong, H.X. Modifying and integrating in vitro and ex vivo respiratory models for inhalation drug screening. Front. Bioeng. Biotechnol., 2020, 8, 581995.
[http://dx.doi.org/10.3389/fbioe.2020.581995] [PMID: 33195144]
[69]
Sciuscio, D.; Hoeng, J.; Peitsch, M.C.; Vanscheeuwijck, P. Respirable aerosol exposures of nicotine dry powder formulations to in vitro, ex vivo, and in vivo pre-clinical models demonstrate consistency of pharmacokinetic profiles. Inhal. Toxicol., 2019, 31(6), 248-257.
[http://dx.doi.org/10.1080/08958378.2019.1662526] [PMID: 31496314]
[70]
Fernandes, C.A.; Vanbever, R. Preclinical models for pulmonary drug delivery. Expert Opin. Drug Deliv., 2009, 6(11), 1231-1245.
[http://dx.doi.org/10.1517/17425240903241788] [PMID: 19852680]
[71]
Sakagami, M.; Byron, P.R.; Venitz, J.; Rypacek, F. Solute disposition in the rat lung in vivo and in vitro: Determining regional absorption kinetics in the presence of mucociliary escalator. J. Pharm. Sci., 2002, 91(2), 594-604.
[http://dx.doi.org/10.1002/jps.10069] [PMID: 11835216]
[72]
Benaouda, F.; Jones, S.A.; Chana, J.; Dal Corno, B.M.; Barlow, D.J.; Hider, R.C.; Page, C.P.; Forbes, B. Ion-pairing with spermine targets theophylline to the lungs via the polyamine transport system. Mol. Pharm., 2018, 15(3), 861-870.
[http://dx.doi.org/10.1021/acs.molpharmaceut.7b00715] [PMID: 29307184]
[73]
Driscoll, K.E.; Costa, D.L.; Hatch, G.; Henderson, R.; Oberdorster, G.; Salem, H.; Schlesinger, R.B. Intratracheal instillation as an exposure technique for the evaluation of respiratory tract toxicity: Uses and limitations. Toxicol. Sci., 2000, 55(1), 24-35.
[http://dx.doi.org/10.1093/toxsci/55.1.24] [PMID: 10788556]
[74]
Tronde, A.; Baran, G.; Eirefelt, S.; Lennernäs, H.; Bengtsson, U.H. Miniaturized nebulization catheters: A new approach for delivery of defined aerosol doses to the rat lung. J. Aerosol Med., 2002, 15(3), 283-296.
[http://dx.doi.org/10.1089/089426802760292627] [PMID: 12396416]
[75]
Tolman, J.A.; Williams, R.O., III Advances in the pulmonary delivery of poorly water-soluble drugs: Influence of solubilization on pharmacokinetic properties. Drug Dev. Ind. Pharm., 2010, 36(1), 1-30.
[http://dx.doi.org/10.3109/03639040903092319] [PMID: 19640248]
[76]
Colthorpe, P.; Farr, S.J.; Taylor, G.; Smith, J.; Wyatt, D. The pharmacokinetics of pulmonary-delivered insulin: A comparison of intratracheal and aerosol administration to the rabbit. Pharm. Res., 1992, 9(6), 764-768.
[http://dx.doi.org/10.1023/A:1015851521551] [PMID: 1409359]
[77]
Niven, R.W.; Whitcomb, K.L.; Shaner, L.; Ip, A.Y.; Kinstler, O.B. The pulmonary absorption of aerosolized and intratracheally instilled rhG-CSF and monoPEGylated rhG-CSF. Pharm. Res., 1995, 12(9), 1343-1349.
[http://dx.doi.org/10.1023/A:1016281925554] [PMID: 8570533]
[78]
Hoppentocht, M.; Hoste, C.; Hagedoorn, P.; Frijlink, H.W.; de Boer, A.H. In vitro evaluation of the DP-4M PennCentury™ insufflator. Eur. J. Pharm. Biopharm., 2014, 88(1), 153-159.
[http://dx.doi.org/10.1016/j.ejpb.2014.06.014] [PMID: 24993307]
[79]
Molina, R.M.; Konduru, N.V.; Hirano, H.; Donaghey, T.C.; Adamo, B.; Laurenzi, B.; Pyrgiotakis, G.; Brain, J.D. Pulmonary distribution of nanoceria: Comparison of intratracheal, microspray instillation and dry powder insufflation. Inhal. Toxicol., 2016, 28(12), 550-560.
[http://dx.doi.org/10.1080/08958378.2016.1226449] [PMID: 27618878]
[80]
Gerde, P.; Ewing, P.; Låstbom, L.; Ryrfeldt, Å.; Waher, J.; Lidén, G. A novel method to aerosolize powder for short inhalation exposures at high concentrations: Isolated rat lungs exposed to respirable diesel soot. Inhal. Toxicol., 2004, 16(1), 45-52.
[http://dx.doi.org/10.1080/08958370490258381] [PMID: 14744664]
[81]
Ewing, P.; Ryrfeldt, Å.; Sjöberg, C.O.; Andersson, P.; Edsbäcker, S.; Gerde, P. Vasoconstriction after inhalation of budesonide: A study in the isolated and perfused rat lung. Pulm. Pharmacol. Ther., 2010, 23(1), 9-14.
[http://dx.doi.org/10.1016/j.pupt.2009.09.004] [PMID: 19800019]
[82]
Schermuly, R.T.; Schulz, A.; Ghofrani, H.A.; Breitenbach, C.S.; Weissmann, N.; Hildebrand, M.; Kurz, J.; Grimminger, F.; Seeger, W. Comparison of pharmacokinetics and vasodilatory effect of nebulized and infused iloprost in experimental pulmonary hypertension: Rapid tolerance development. J. Aerosol Med., 2006, 19(3), 353-363.
[http://dx.doi.org/10.1089/jam.2006.19.353] [PMID: 17034310]
[83]
Forbes, B.; Asgharian, B.; Dailey, L.A.; Ferguson, D.; Gerde, P.; Gumbleton, M.; Gustavsson, L.; Hardy, C.; Hassall, D.; Jones, R.; Lock, R.; Maas, J.; McGovern, T.; Pitcairn, G.R.; Somers, G.; Wolff, R.K. Challenges in inhaled product development and opportunities for open innovation. Adv. Drug Deliv. Rev., 2011, 63(1-2), 69-87.
[http://dx.doi.org/10.1016/j.addr.2010.11.004] [PMID: 21144875]
[84]
Naeije, R.; Westerhof, N. Pulmonary Vascular Disease. Textbook of Pulmonary Vascular Disease; Springer: Boston, US, 2011.
[85]
Vanderpool, R.R.; Naeije, R.; Chesler, N.C. Impedance in isolated mouse lungs for the determination of site of action of vasoactive agents and disease. Ann. Biomed. Eng., 2010, 38(5), 1854-1861.
[http://dx.doi.org/10.1007/s10439-010-9960-2] [PMID: 20162354]
[86]
Ketabchi, F.; Karimi, Z.S.; Moosavi, S.M. Sustained hypoxic pulmonary vasoconstriction in the isolated perfused rat lung: Effect of α1-adrenergic receptor agonist. Iran. J. Med. Sci., 2014, 39(3), 275-281.
[PMID: 24850985]
[87]
Yoo, H.Y.; Zeifman, A.; Ko, E.A.; Smith, K.A.; Chen, J.; Machado, R.F.; Zhao, Y.Y.; Minshall, R.D.; Yuan, J.X.J. Optimization of isolated perfused/ventilated mouse lung to study hypoxic pulmonary vasoconstriction. Pulm. Circ., 2013, 3(2), 396-405.
[http://dx.doi.org/10.4103/2045-8932.114776] [PMID: 24015341]
[88]
Eriksson, J.; Sjögren, E.; Lennernäs, H.; Thörn, H. Drug absorption parameters obtained using the isolated perfused rat lung model are predictive of rat in vivo lung absorption. AAPS J., 2020, 22(3), 71.
[http://dx.doi.org/10.1208/s12248-020-00456-x] [PMID: 32394314]
[89]
Ewing, P.; Eirefelt, S.J.; Andersson, P.; Blomgren, A.; Ryrfeldt, Å.; Gerde, P. 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., 2008, 21(2), 169-180.
[http://dx.doi.org/10.1089/jamp.2007.0654] [PMID: 18518793]
[90]
Pang, Y.; Sakagami, M.; Byron, P.R. The pharmacokinetics of pulmonary insulin in the in vitro isolated perfused rat lung: Implications of metabolism and regional deposition. Eur. J. Pharm. Sci., 2005, 25(4-5), 369-378.
[http://dx.doi.org/10.1016/j.ejps.2005.03.010] [PMID: 15979534]
[91]
Pang, Y.; Sakagami, M.; Byron, P.R. Insulin self-association: Effects on lung disposition kinetics in the airways of the isolated perfused rat lung (IPRL). Pharm. Res., 2007, 24(9), 1636-1644.
[http://dx.doi.org/10.1007/s11095-007-9292-6] [PMID: 17476466]
[92]
Byron, P.R.; Roberts, S.R.N.; Clark, A.R. An isolated perfused rat lung preparation for the study of aerosolized drug deposition and absorption. J. Pharm. Sci., 1986, 75(2), 168-171.
[http://dx.doi.org/10.1002/jps.2600750214] [PMID: 3958927]
[93]
Manford, F.; Tronde, A.; Jeppsson, A.B.; Patel, N.; Johansson, F.; Forbes, B. Drug permeability in 16HBE14o- airway cell layers correlates with absorption from the isolated perfused rat lung. Eur. J. Pharm. Sci., 2005, 26(5), 414-420.
[http://dx.doi.org/10.1016/j.ejps.2005.07.010] [PMID: 16153810]
[94]
Ritchie, T.J.; Luscombe, C.N.; Macdonald, S.J.F. Analysis of the calculated physicochemical properties of respiratory drugs: Can we design for inhaled drugs yet? J. Chem. Inf. Model., 2009, 49(4), 1025-1032.
[http://dx.doi.org/10.1021/ci800429e] [PMID: 19275169]
[95]
Edwards, C.D.; Luscombe, C.; Eddershaw, P.; Hessel, E.M. Development of a novel quantitative structure-activity relationship model to accurately predict pulmonary absorption and replace routine use of the isolated perfused respiring rat lung model. Pharm. Res., 2016, 33(11), 2604-2616.
[http://dx.doi.org/10.1007/s11095-016-1983-4] [PMID: 27401409]
[96]
Bitonti, A.J.; Dumont, J.A. Pulmonary administration of therapeutic proteins using an immunoglobulin transport pathway. Adv. Drug Deliv. Rev., 2006, 58(9-10), 1106-1118.
[http://dx.doi.org/10.1016/j.addr.2006.07.015] [PMID: 16997417]
[97]
Sakagami, M.; Omidi, Y.; Campbell, L.; Kandalaft, L.E.; Morris, C.J.; Barar, J.; Gumbleton, M. Expression and transport functionality of FcRn within rat alveolar epithelium: A study in primary cell culture and in the isolated perfused lung. Pharm. Res., 2006, 23(2), 270-279.
[http://dx.doi.org/10.1007/s11095-005-9226-0] [PMID: 16382279]
[98]
Gumbleton, M.; Al-Jayyoussi, G.; Crandon-Lewis, A.; Francombe, D.; Kreitmeyr, K.; Morris, C.J.; Smith, M.W. Spatial expression and functionality of drug transporters in the intact lung: Objectives for further research. Adv. Drug Deliv. Rev., 2011, 63(1-2), 110-118.
[http://dx.doi.org/10.1016/j.addr.2010.09.008] [PMID: 20868712]
[99]
Ambudkar, S.V.; Dey, S.; Hrycyna, C.A.; Ramachandra, M.; Pastan, I.; Gottesman, M.M. Biochemical, cellular, and pharmacological aspects of the multidrug transporter. Annu. Rev. Pharmacol. Toxicol., 1999, 39(1), 361-398.
[http://dx.doi.org/10.1146/annurev.pharmtox.39.1.361] [PMID: 10331089]
[100]
Kuhlmann, O.; Hofmann, H.S.; Müller, S.P.; Weiss, M. Pharmacokinetics of idarubicin in the isolated perfused rat lung: Effect of cinchonine and rutin. Anticancer Drugs, 2003, 14(6), 411-416.
[http://dx.doi.org/10.1097/00001813-200307000-00004] [PMID: 12853881]
[101]
Roerig, D.L.; Audi, S.H.; Ahlf, S.B. Kinetic characterization of P-glycoprotein-mediated efflux of rhodamine 6G in the intact rabbit lung. Drug Metab. Dispos., 2004, 32(9), 953-958.
[http://dx.doi.org/10.1124/dmd.104.000042] [PMID: 15319336]
[102]
Sakagami, M.; Gumbleton, M. Targeted drug delivery through the respiratory system: molecular control on lung absorption and disposition. In: Controlled Pulmonary Drug Delivery; Smyth, H.D.C.; Hickey, A.J., Eds.; Springer: New York, 2011; pp. 127-141.
[http://dx.doi.org/10.1007/978-1-4419-9745-6_6]
[103]
Al-Jayyoussi, G.; Price, D.F.; Francombe, D.; Taylor, G.; Smith, M.W.; Morris, C.; Edwards, C.D.; Eddershaw, P.; Gumbleton, M. Selectivity in the impact of P-glycoprotein upon pulmonary absorption of airway-dosed substrates: A study in ex vivo lung models using chemical inhibition and genetic knockout. J. Pharm. Sci., 2013, 102(9), 3382-3394.
[http://dx.doi.org/10.1002/jps.23587] [PMID: 23670704]
[104]
Price, D.F.; Luscombe, C.N.; Eddershaw, P.J.; Edwards, C.D.; Gumbleton, M. The differential absorption of a series of P-glycoprotein substrates in isolated perfused lungs from mdr1a/1b genetic knockout mice can be attributed to distinct physico-chemical properties: An insight into predicting transporter-mediated, pulmonary specific disposition. Pharm. Res., 2017, 34(12), 2498-2516.
[http://dx.doi.org/10.1007/s11095-017-2220-5] [PMID: 28702798]
[105]
Bosquillon, C. Drug transporters in the lung-do they play a role in the biopharmaceutics of inhaled drugs? J. Pharm. Sci., 2010, 99(5), 2240-2255.
[http://dx.doi.org/10.1002/jps.21995] [PMID: 19950388]
[106]
Salomon, J.J.; Ehrhardt, C. Organic cation transporters in the blood-air barrier: Expression and implications for pulmonary drug delivery. Ther. Deliv., 2012, 3(6), 735-747.
[http://dx.doi.org/10.4155/tde.12.51] [PMID: 22838069]
[107]
Gnadt, M.; Trammer, B.; Freiwald, M.; Kardziev, B.; Bayliss, M.K.; Edwards, C.D.; Schmidt, M.; Friedel, G.; Högger, P. Methacholine delays pulmonary absorption of inhaled β2-agonists due to competition for organic cation/carnitine transporters. Pulm. Pharmacol. Ther., 2012, 25(1), 124-134.
[http://dx.doi.org/10.1016/j.pupt.2011.12.009] [PMID: 22245488]
[108]
Al-Jayyoussi, G.; Price, D.F.; Kreitmeyr, K.; Keogh, J.P.; Smith, M.W.; Gumbleton, M.; Morris, C.J. Absorption of ipratropium and l -carnitine into the pulmonary circulation of the ex vivo rat lung is driven by passive processes rather than active uptake by OCT/OCTN transporters. Int. J. Pharm., 2015, 496(2), 834-841.
[http://dx.doi.org/10.1016/j.ijpharm.2015.10.036] [PMID: 26475971]
[109]
Rannels, D.E.; Pegg, A.E.; Clark, R.S.; Addison, J.L. Interaction of paraquat and amine uptake by rat lungs perfused in situ. Am. J. Physiol., 1985, 249(5 Pt 1), E506-E513.
[PMID: 4061640]
[110]
Martínez, M.S.M.; Gandarillas, C.I.C.; Lanao, J.M.; Navarro, A.S. Comparative study of the disposition of levofloxacin, netilmicin and cefepime in the isolated rat lung. J. Pharm. Pharmacol., 2010, 57(7), 861-867.
[http://dx.doi.org/10.1211/0022357056479] [PMID: 15969945]
[111]
Reinoso, R.F.; Sánchez-Navarro, A.; Lanao, J.M. Distribution of ciprofloxacin in the isolated rat lung in the presence and absence of tissue oedema. Eur. J. Pharm. Sci., 1999, 8(3), 203-209.
[http://dx.doi.org/10.1016/S0928-0987(99)00011-1] [PMID: 10379043]
[112]
de Jesús Valle, M.J.; Uranga, N.S.; López, F.G.; Hurlé, A.D.G.; Navarro, A.S. Disposition of linezolid in the isolated rat lung after systemic and pulmonary drug delivery. J. Antimicrob. Chemother., 2007, 60(5), 1074-1079.
[http://dx.doi.org/10.1093/jac/dkm306] [PMID: 17827144]
[113]
de Jesús Valle, M.J.; López, F.G.; Hurlé, A.D.G.; Navarro, A.S. Pulmonary versus systemic delivery of antibiotics: Comparison of vancomycin dispositions in the isolated rat lung. Antimicrob. Agents Chemother., 2007, 51(10), 3771-3774.
[http://dx.doi.org/10.1128/AAC.00099-07] [PMID: 17682107]
[114]
Jesús Valle, M.J.; González López, F.; Sánchez Navarro, A. Pulmonary versus systemic delivery of levofloxacin. Pulm. Pharmacol. Ther., 2008, 21(2), 298-303.
[http://dx.doi.org/10.1016/j.pupt.2007.07.003] [PMID: 17869149]
[115]
Vane, J.R. The release and fate of vaso-active hormones in the circulation. Br. J. Pharmacol., 1969, 35(2), 209-242.
[http://dx.doi.org/10.1111/j.1476-5381.1969.tb07982.x] [PMID: 4388134]
[116]
Hartiala, J.; Uotila, P.; Nienstedt, W. Metabolism of progesterone in the isolated perfused rat lungs. J. Steroid Biochem., 1979, 11(5-6), 1539-1541.
[http://dx.doi.org/10.1016/0022-4731(79)90345-5] [PMID: 522468]
[117]
Hartiala, J.; Uotila, P.; Nienstedt, W. Metabolism of testosterone in the isolated perfused rat lungs. J. Steroid Biochem., 1976, 7(6-7), 527-533.
[http://dx.doi.org/10.1016/0022-4731(76)90213-2] [PMID: 966765]
[118]
Hartiala, J.; Uotila, P.; Nienstedt, W. Metabolism of estradiol in isolated perfused rat lungs. J. Steroid Biochem., 1980, 13(5), 571-572.
[http://dx.doi.org/10.1016/0022-4731(80)90216-2] [PMID: 7392633]
[119]
Sharma, R.; Kodavanti, U.P.; Smith, L.L.; Mehendale, H.M. The uptake and metabolism of cystamine and taurine by isolated perfused rat and rabbit lungs. Int. J. Biochem. Cell Biol., 1995, 27(7), 655-664.
[http://dx.doi.org/10.1016/1357-2725(95)00038-Q] [PMID: 7648421]
[120]
Rubin, K.; Ewing, P.; Bäckström, E.; Abrahamsson, A.; Bonn, B.; Kamata, S.; Grime, K. Pulmonary metabolism of substrates for key drug-metabolizing enzymes by human alveolar type II cells, human and rat lung microsomes, and the isolated perfused rat lung model. Pharmaceutics, 2020, 12(2), 117.
[http://dx.doi.org/10.3390/pharmaceutics12020117] [PMID: 32024122]
[121]
Baker, D.G.; Toth, B.R.; Goad, M.E.P.; Barker, S.A.; Means, J.C. Establishment and validation of an isolated rat lung model for pulmonary metabolism studies. J. Appl. Toxicol., 1999, 19(2), 83-91.
[http://dx.doi.org/10.1002/(SICI)1099-1263(199903/04)19:2<83:AID-JAT541>3.0.CO;2-Y] [PMID: 10215180]
[122]
Foth, H.; Geng, W.P.; Krug, N.; Vetterlein, F. Pulmonary uptake of bupivacaine in isolated perfused rat lung. Naunyn Schmiedebergs Arch. Pharmacol., 1995, 351(1), 99-106.
[http://dx.doi.org/10.1007/BF00169070] [PMID: 7715747]
[123]
Mobley, C.; Hochhaus, G. Methods used to assess pulmonary deposition and absorption of drugs. Drug Discov. Today, 2001, 6(7), 367-375.
[http://dx.doi.org/10.1016/S1359-6446(01)01691-9] [PMID: 11267923]
[124]
Cooper, A.E.; Ferguson, D.; Grime, K. Optimisation of DMPK by the inhaled route: Challenges and approaches. Curr. Drug Metab., 2012, 13(4), 457-473.
[http://dx.doi.org/10.2174/138920012800166571] [PMID: 22299825]
[125]
Beck-Broichsitter, M.; Gauss, J.; Gessler, T.; Seeger, W.; Kissel, T.; Schmehl, T. Pulmonary targeting with biodegradable salbutamol-loaded nanoparticles. J. Aerosol Med. Pulm. Drug Deliv., 2010, 23(1), 47-57.
[http://dx.doi.org/10.1089/jamp.2009.0759] [PMID: 19778266]
[126]
Bayard, F.J.C.; Thielemans, W.; Pritchard, D.I.; Paine, S.W.; Young, S.S.; Bäckman, P.; Ewing, P.; Bosquillon, C. Polyethylene glycol-drug ester conjugates for prolonged retention of small inhaled drugs in the lung. J. Control. Release, 2013, 171(2), 234-240.
[http://dx.doi.org/10.1016/j.jconrel.2013.07.023] [PMID: 23916883]
[127]
Chen, X.; Huang, W.; Wong, B.C.; Yin, L.; Wong, Y.F.; Xu, M.; Yang, Z. Liposomes prolong the therapeutic effect of anti-asthmatic medication via pulmonary delivery. Int. J. Nanomedicine, 2012, 7, 1139-1148.
[PMID: 22412300]
[128]
Oh, Y.J.; Lee, J.; Seo, J.Y.; Rhim, T.; Kim, S.H.; Yoon, H.J.; Lee, K.Y. Preparation of budesonide-loaded porous PLGA microparticles and their therapeutic efficacy in a murine asthma model. J. Control. Release, 2011, 150(1), 56-62.
[http://dx.doi.org/10.1016/j.jconrel.2010.11.001] [PMID: 21070826]
[129]
Morris, C.J.; Smith, M.W.; Griffiths, P.C.; McKeown, N.B.; Gumbleton, M. Enhanced pulmonary absorption of a macromolecule through coupling to a sequence-specific phage display-derived peptide. J. Control. Release, 2011, 151(1), 83-94.
[http://dx.doi.org/10.1016/j.jconrel.2010.12.003] [PMID: 21182881]
[130]
Zhang, J.; Wu, L.; Chan, H.K.; Watanabe, W. Formation, characterization, and fate of inhaled drug nanoparticles. Adv. Drug Deliv. Rev., 2011, 63(6), 441-455.
[http://dx.doi.org/10.1016/j.addr.2010.11.002] [PMID: 21118707]
[131]
Martin, A.R.; Thompson, R.B.; Finlay, W.H. MRI measurement of regional lung deposition in mice exposed nose-only to nebulized superparamagnetic iron oxide nanoparticles. J. Aerosol Med. Pulm. Drug Deliv., 2008, 21(4), 335-342.
[http://dx.doi.org/10.1089/jamp.2008.0698] [PMID: 18800881]
[132]
Hamoir, J.; Nemmar, A.; Halloy, D.; Wirth, D.; Vincke, G.; Vanderplasschen, A.; Nemery, B.; Gustin, P. Effect of polystyrene particles on lung microvascular permeability in isolated perfused rabbit lungs: Role of size and surface properties. Toxicol. Appl. Pharmacol., 2003, 190(3), 278-285.
[http://dx.doi.org/10.1016/S0041-008X(03)00192-3] [PMID: 12902199]
[133]
Nemmar, A.; Hamoir, J.; Nemery, B.; Gustin, P. Evaluation of particle translocation across the alveolo-capillary barrier in isolated perfused rabbit lung model. Toxicology, 2005, 208(1), 105-113.
[http://dx.doi.org/10.1016/j.tox.2004.11.012] [PMID: 15664437]
[134]
Meiring, J.J.; Borm, P.J.A.; Bagate, K.; Semmler, M.; Seitz, J.; Takenaka, S.; Kreyling, W.G. The influence of hydrogen peroxide and histamine on lung permeability and translocation of iridium nanoparticles in the isolated perfused rat lung. Part. Fibre Toxicol., 2005, 2(1), 3.
[http://dx.doi.org/10.1186/1743-8977-2-3] [PMID: 15982423]
[135]
Oberdörster, G.; Sharp, Z.; Atudorei, V.; Elder, A.; Gelein, R.; Lunts, A.; Kreyling, W.; Cox, C. Extrapulmonary translocation of ultrafine carbon particles following whole-body inhalation exposure of rats. J. Toxicol. Environ. Health A, 2002, 65(20), 1531-1543.
[http://dx.doi.org/10.1080/00984100290071658] [PMID: 12396867]
[136]
Beck-Broichsitter, M.; Gauss, J.; Packhaeuser, C.B.; Lahnstein, K.; Schmehl, T.; Seeger, W.; Kissel, T.; Gessler, T. Pulmonary drug delivery with aerosolizable nanoparticles in an ex vivo lung model. Int. J. Pharm., 2009, 367(1-2), 169-178.
[http://dx.doi.org/10.1016/j.ijpharm.2008.09.017] [PMID: 18848609]
[137]
Beck-Broichsitter, M.; Stoisiek, K.; Bohr, A.; Aragão-Santiago, L.; Gessler, T.; Seeger, W.; Kissel, T. Potential of the isolated lung technique for the examination of sildenafil absorption from lung-delivered poly(lactide- co -glycolide) microparticles. J. Control. Release, 2016, 226, 15-20.
[http://dx.doi.org/10.1016/j.jconrel.2016.01.057] [PMID: 26849917]
[138]
Dong, M.; Mürdter, T.E.; Philippi, C.; Loretz, B.; Schaefer, U.F.; Lehr, C.M.; Schwab, M.; Ammon-Treiber, S. Pulmonary delivery and tissue distribution of aerosolized antisense 2′-O-methyl RNA containing nanoplexes in the isolated perfused and ventilated rat lung. Eur. J. Pharm. Biopharm., 2012, 81(3), 478-485.
[http://dx.doi.org/10.1016/j.ejpb.2012.04.022] [PMID: 22565122]
[139]
Ong, H.X.; Benaouda, F.; Traini, D.; Cipolla, D.; Gonda, I.; Bebawy, M.; Forbes, B.; Young, P.M. In vitro and ex vivo methods predict the enhanced lung residence time of liposomal ciprofloxacin formulations for nebulisation. Eur. J. Pharm. Biopharm., 2014, 86(1), 83-89.
[http://dx.doi.org/10.1016/j.ejpb.2013.06.024] [PMID: 23851077]

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