Pulmonary drug delivery: Physiologic and mechanistic aspects

Critical Reviews in Therapeutic Drug Carrier Systems

Volumn 14, Issue 4, 1997, Pages 395-453

  Yu, Jianwei ^a   Chien, Yie W ^a  

^a RUTGERS UNIVERSITY   (United States)

Author keywords

Peptides; Proteins; Pulmonary absorption; Pulmonary delivery; Respiratory structure

Indexed keywords

BACITRACIN; CALCITONIN; CARBOXYMETHYLCELLULOSE; DETIRELIX; DEXTRAN; EDETIC ACID; GLYCOCHOLIC ACID; INSULIN; LEUPRORELIN; LIPOSOME; MACROGOL; NAFAMSTAT; PYRANOSIDE; RECOMBINANT GRANULOCYTE COLONY STIMULATING FACTOR; SALICYLIC ACID; SORBITAN TRIOLEATE; SURFACTIN;

CONTROLLED RELEASE FORMULATION; DRUG ABSORPTION; DRUG DELIVERY SYSTEM; DRUG DISPOSITION; DRUG ELIMINATION; DRUG FORMULATION; DRUG SOLUBILITY; DRUG UPTAKE; DRY POWDER; GENE TECHNOLOGY; HUMAN; INHALATIONAL DRUG ADMINISTRATION; INTRATRACHEAL DRUG ADMINISTRATION; INTRAVENOUS DRUG ADMINISTRATION; LUNG ALVEOLUS SURFACE TENSION; LUNG CAPILLARY; LUNG LYMPH; LUNG VENTILATION PERFUSION RATIO; METERED DOSE INHALER; NEBULIZATION; NONHUMAN; RESPIRATORY TRACT MUCOSA; REVIEW; SUBCUTANEOUS DRUG ADMINISTRATION;

EID: 0031454495     PISSN: 07434863     EISSN: None     Source Type: Journal    
DOI: 10.1615/critrevtherdrugcarriersyst.v14.i4.20     Document Type: Review

References (152)

1. Wigley, F. M., Londono, J. H., Wood, S. H., Shipp, J. C., and Waldman, R. H., Insulin across respiratory mucosae by aerosol delivery, Diabetes, 20, 552, 1971.
2. Weibel, E. R., Morphometry of the Human Lung, Springer Verlag, Berlin, 1963.
3. Sleigh, M. A., The nature and action of respiratory tract cilia. In: Brain, J.D., Proctor, D.F., and Reid L.M. (Eds), Respiratory Defense Mechanisms, Part 1. Marcel Dekker, New York, 247, 1977.
4. Robertson, B., Basic morphology of the pulmonary defense system, Eur. J. Respir. Dis., 61 (suppl. 107), 21, 1980.
5. Weibel, E. R., Morphometrics of the human lung, Handbk. Physiol., Section 3, 1, 285, 1964.
6. Inoue, S. and Jogg, J., Intercellular junctions of the tracheal epithelium in guinea pigs, Lab. Invest., 31, 68, 1974.
7. Angus, G. E. and Thurlbeck, W. M., Number of alveoli in the human lung, J. Appl. Physiol., 32, 483, 1972.
8. Glazier, J. B., Hughes, J. M. B., Maloney, J. E., and West, J. B., Vertical gradient of alveolar size in lungs of dogs frozen intact, J. Appl. Physiol., 23, 694, 1967.
9. Liebow, A. A., Recent advances in pulmonary anatomy. In: Pulmonary Structure and Function, deReuk, A. V. S. and O'Connor, M. (Eds), Churchill Livingstone, Edingburgh and London, 1962.
10. Lambert, M. W., Accessory bronchiole-alveolar communication, J. Path. Bact., 70, 31, 1955.
11. Weibel, E. R., Morphological basis of alveolar-capillary gas exchange, Physiol. Rev., 53, 419, 1973.
12. Hills, B. A., What forces keep the air spaces of the lung dry? Thorax, 37, 713, 1982.
13. Dunhill, M. S., In: New Directions in Asthma (Stein, M., ed.), American College of Chest Physicians, Illinois, 213, 1975.
14. Weibel, E. R., Pathway for Oxygen. Harvard University Press, Cambridge, 1984.
15. DeFouw, D. O., Ultrastructural features of alveolar epithelial transport, Am. Rev. Respir. Dis., 127, S9, 1983.
16. Nash, G., Blennerhassett, J. B., and Pontoppidan, H., Pulmonary lesions associated with oxygen therapy and artificial ventilation, New Eng. J. Med., 276, 368, 1967.
17. Leake, E. S. and Heise, E. R., Comparative cytology of alveolar and peritoneal macrophages from germ free rats. The reticuloendothelial system and atherosclerosis. In: Diluzio, N.R. and Paoletti, R. (Eds), Advances in Experimental Medicine and Biology. Vol. 1. New York: Plenum Press, 1967, 136.
18. Dannenberg, A. M., Burstone, M. S., Walter, P. C., and Kinsley, J. W., A histochemical study of phagocytic and enzymatic function of rabbit mononuclear and polymorphonuclear exudate cells and alveolar macrophages. I. Survey and quantitation of enzymes, and states of cellular activation, J. Cell Biol., 17, 465, 1963.
19. Oren, R., Farham, A. E., Saito, K., Milofsky, E., and Karnosvsky, M. L., Metabolic patterns in three types of phagocytizing cells, J. Cell Biol., 17, 487, 1963.
20. Babior, B. M., Kipnes, R. S., and Curnutte, J. T., The production by leukocytes of superoxide, a potential bactericidal agent, J. Clin. Invest., 52, 741, 1973.
21. Shneeberger-Keeley, E. E. and Karnovsky, M.J., The ultrastructural basis of alveolar-capillary membrane permeability to peroxidase used as tracer, J. Cell Biol., 37, 781, 1968.
22. Ryan, U. S., Structural basis for metabolic activity, Ann. Rev. Physiol., 44, 223, 1982.
23. Ryan, U. S., Metabolic activity of pulmonary endothelium, Ann. Rev. Physiol., 48, 263, 1986.
24. Strum, J. M. and junod, A. F., Radioautographic demonstration of 5-hydroxytryptamine-3H uptake by pulmonary endothelial Cells, J. Cell Biol., 54, 456, 1972.
25. Smith, S. and Ryan, J. W., An electron microscopic study of the vascular endothelium as a site for bradykinin and adenosine-5-triphosphate inactivation in rat lung. In: Bradykinin and Related Kinins. Plenum Press, New York, 249, 1970.
26. Smith, U. and Ryan, J. W., Pulmonary endothelial cells and the metabolism of adenine nucleotides, linins and angiotensin I. In: Vasopeptides, Chemistry, Pharmacology and Pathophysiology, by Buck, N. and Sicuteri, F. (Eds), Plenum Publishing Co., New York, 267, 1973.
27. Ryan, J. W., Smith, U., and Niemeyer, R. S., Angiotensin I. Metabolism by plasma membrane of lung, Science, 176, 64, 1972.
28. Ryan J. W., Processing of endogenous polypeptides by the lungs, Ann. Rev. Physiol., 44, 241, 1982.
29. Piper, P.J., Vane, J. R., and Willie, J. H., Inactivation of prostaglandins by the lungs, Nature, 225, 600, 1970.
30. Davies, P. Jones, R. C., Schloo, B. L., and Reid, L. M., Endothelium of the pulmonary vasculature in health and disease, In: Pulmonary Endothelium in Health and Disease. Edited by Ryan, U.S., 375, 1987.
31. Duke, H. N., The site of action of anoxia on the pulmonary blood vessels of the cat, J. Physiol., 125, 373, 1954.
32. Staub, N. C., The interdependence of pulmonary structure and function, Anesthesiology, 24, 831, 1963.
33. West, J. B., Blood flow to the lung and gas exchange. Anesthesiology, 41, 124, 1974.
34. Staub, N. C., Pulmonary oedema, Physiol. Rev., 54, 679, 1974.
35. Sanderson, M. J. and Sleigh, M. A., Ciliary activity of cultured rabbit tracheal epithelium: beat pattern and metachrony, J. Cell Sci., 47, 331, 1981.
36. King, M., Gilboa, A., Meyer, F. A., and Silbergerg, A., On the transport of mucus and its rheologic simulants in ciliated system, Rev. Respir. Dis., 110, 740, 1974.
37. Litt, M., Mucus rheology and mucociliary clearance, Mod. Probl. Paediatr., 19, 175, 1977.
38. Colacicco, G., Arguments against and alternatives for an extracellular surfactant layer in the alveoli of mammalian lung, J. Theor. Biol., 114, 641, 1985.
39. Galdston, M. and Shah, D.O., Surface properties and hysteresis of dipalmitoyllecithin in relation to the alveolar lining layer. Biochim. Biophys. Acta., 137, 125, 1967.
40. Hills, B. A., The Biology of Surfactant. Cambridge University Press, Cambridge, 1988.
41. Hills, B. A., Water repellency induced by pulmonary surfactants, J, Physiol., 325, 175, 1982b.
42. Pattle, R, E., Properties, function and origin of the alveoli lining layer. Nature, 175, 1125, 1955.
43. Niemen, G, F., Bredenberg, C, E., Clark, W, R., and West, N, R., Alveolar function following surfactant deactivation. J, Appl, Physiol., 51, 895, 1981.
44. Guyton, A, C., Moffat, D, S., and Adair,T, H., Role of alveolar surface tension in transepithelial movement of fluid, In: Pulmonary Surfactant, Robertson, B., van Golde, L.M.G, and Batenburg, J.J, (Eds), Elsevier, Amsterdam, 171, 1984.
45. Robertson, B., Berry, D., Curstedt, T., Grossmann, G., Ikegami, M. Jacobs, H., and Jobe, A., Leakage of protein in the immature rabbit lung: effect of surfactant replacement, Respir. Physiol., 61, 625, 1985.
46. Jobe, A., Ikegami, M., Jocobs, H., Jones, S., and Conaway, D., Permeability of premature lamb lungs to protein and effect of surfactant on that permeability, J. Appl. Physiol., 55, 169, 1983.
47. 3H in alveolar type II pneumocytes in relation to surfactant synthesis. A quantitative radiographic study in mouse by electron microscopy, Anat. Rec., 174, 289, 1972.
48. Macklin, C. C., The pulmonary alveolar mucoid film and the pneumocytes, Lancet, 1, 1099, 1954.
49. Levitzky, M. G., Pulmonary Physiology. 3rd edition, New York: McGraw-Hill, 1991, 51.
50. Pietak, S., Weenig, C. S., Hickey, R. E., and Fairly, H. B., Anesthetic effect on ventilation in patients with chronic obstructive pulmonary disease, Anesthesiology, 42, 160, 1975.
51. West, J. B., Regional differences in gas exchange in the lung of erect man, J. Appl. Physiol., 17, 893, 1962.
52. Hughes, J. M. B., Grant, B.J. B, Greene, R. E., Iliff, L. D., and Milic-Emili, J., Inspiratory flow rate and ventilation distribution in normal subjects and in patients with simple chronic bronchitis, Clin. Sci., 43, 583, 1972.
53. West, J. B., Dollery, C. T., and Naimark, A., Distribution of blood flow in isolated lung: relation to vascular and alveolar pressures, J. Appl. Physiol., 19, 713, 1964.
54. Michels, D. B. and West, J. B., Distribution of pulmonary ventilation and perfusion during short periods of weightlessness, J. Appl. Physiol., 45, 987, 1978.
55. West, J. B, Dollery, C. T., and Naimark, A., Distribution of blood flow in isolated lung: relation to vascular and alveolar pressures, J. Appl. Physiol., 19, 713, 1964.
56. West, J. B, Dollery, C. T., Distribution of blood flow and the pressure-flow relations of the whole lung, J. Appl. Physiol., 20, 175, 1965.
57. Hughes, J. M. B., Glazier, J. B., Maloney, J. E., and West, J. B., Effect of lung volume on the distribution of pulmonary blood flow in man, Respir. Physiol., 4, 58, 1968.
58. West, J. B., Radioactive methods and blood flow. In: West, J. B. (Ed), Regional Differences in the Lung., Academic, New York, 34, 1977.
59. 2, J. Clin. Invest., 54, 54, 1974.
60. Wagner, P. D., Laravuso, R. B., Goldzimmer, E., Naumann, P. F., and West, J. B., Distribution of ventilation-perfusion ratios in dogs in normal and abnormal lungs, J. Appl. Physiol., 38, 1099, 1975.
61. Niemeier, R. W. and Bingham, E., An isolated perfused lung preparation for metabolic studies. Life Sci. Part II. Biochem. Gen. Mol Biol., 11, 807, 1972.
62. Brazzell, R. K., Smith, R. B., and Kostenbauder, H. B., Isolated perfused rabbit lung as a model for intravascular and intrabronchial administration of bronchodilator drugs I: Isoproterenol, J. Pharm. Sci., 71, 1268, 1982.
63. Brazzell, R. K., and Kostenbauder, H. B., Isolated perfused rabbit lung as a model for intravascular and intrabronchial administration of bronchodilator drugs II: Isoproterenol Prodrugs, J. Pharm. Sci, 71, 1274, 1982.
64. Byron, P. R., Roberts, N. S. R., and Clark A. R., An isolated perfused rat lung preparation for the study of aerosolized drug deposition and absorption, J. Pharm. Sci., 75, 168, 1986.
65. Byron, P. R and Niven, R. W., A novel dosing method for drug administration to the airways of the isolated perfused rat lung, J. Pharm. Sci., 77, 693, 1988.
66. Orten, T. C., Anderson, M. W., Pickett, R. D., Eling, T. E., and Fouts J. R., Xenobiotic accumulation and metabolism by isolated perfused rabbit lungs, J. Pharmacol. Exp. Ther., 186, 482, 1973.
67. Law, F. C. P., Eling, T. E., Bend, J. R., and Fouts, J. R., Metabolism of xenobiotics by the isolated perfused lung, Drug Metab. Dispos., 2, 433, 1974.
68. McGovern, J. P., Lubawy W. C., and Kostenbauder, H. B., Uptake and metabolism of nicotine by the isolated perfused rabbit lung, J. Pharmacol. Exp. Ther., 199, 198, 1976.
69. Cardoso, P. F. G., Mayer, M. S. E., Shi, S. Q., Pop, R. D., Puskas, J., Perrier, D., Tong, J., Baines, A. D., and Patterson, G. A., Use of isolated in situ canine lung perfusion model to evaluate dopamine clearance by the lung, J. Pharmacol. Exp. Ther., 259, 1271, 1991.
70. Ratto, G. B., Esposito, M., Leprini, A., Civalleri, D., Cian, F. D., Vannozzi, M. O., Romano, P., Canepa, M., and Zaccheo, D., In situ lung perfusion with cisplatin. An experimental study, Cancer, 71, 2962, 1993.
71. Brown, R. A. and Schanker, L. S., Absorption of aerosolized drugs from the rat lung, Drug Metab. Dispos., 11, 355, 1983.
72. Schanker, L. S. and Burton, J. A., Absorption of heparin and cyanocobalamin from the rat lung, Proc. Soc. Exp. Biol. Med., 152, 377, 1976.
73. Cheek, J. M., Evans, M. J., and Crandall, E. D., Type I cell-like morphology in tight alveolar epithelial monolayers, Exp. Cell Res., 184, 375, 1989.
74. - fluxes to net ion transport by alveolar epithelium, Respir. Physiol., 85, 245, 1991.
75. Kim, K. J., Suh, D. J., Lubman, R. L., Danto, S. L., Borok, Z., and Crandall, E. D., Ion fluxes across alveolar epithelial cell monolayers, J. Tiss. Cult. Meth., 14, 187, 1992.
76. Fujita, T., Yamamoto, A., and Muranishi, S., Comparison of permeability of macromolecular drugs across cultured intestinal and alveolar epithelial cell lines, International Symposium, Delivery of Protein Drugs: The Next 10 Years, September 4-9, 1993, Kyoto, Japan.
77. Brain, J. D., Knudson, D. E., Sorokin, S. P., and Davis M.A., Pulmonary distribution of particles given by intratracheal instillation or by aerosol inhalation, Environ. Res., 11, 13, 1976.
78. Brain, J. D. and Valberg, P. A., Deposition of aerosol in the respiratory tract, Am. Rev. Respir. Dis., 120, 1325, 1979.
79. Colthorpe, P. Farr, S. J., Tayler, G., Smith, I. J., and Wyatt, D., The pharmacokinetics of pulmonary delivered insulin: a comparison of intratracheal instillation and aerosol administration to the rabbit, Pharm. Res., 9, 764, 1991.
80. Pritchard, J.N., Homes, A., Evans, R.J., and Morgan, A., The distribution of dust in the rat lung following administration by inhalation and by single intratracheal instillation, Environ. Res., 36, 268, 1985.
81. O'Doherty, M.J., Thomas, S.H.L., Page, C.J., Treacher, D.F., and Nunan, T.O., Delivery of a nebulized aerosol to a lung model during mechanical ventilation. Effect of ventilator settings and nebulizer type; position and volume of fill, Am. Rev. Respir. Dis., 146, 383, 1992.
82. Thomas, S.H.L., O'Doherty, M.J., Page, C.J., Treacher, D.F., and Nunan,T.O., Delivery of ultrasonic nebulized aerosols to a lung model during mechanical ventilation, Am. Rev. Respir. Dis., 148, 872, 1993.
83. Maclntyre, N. R., Silver, R. M., Miller, C. W., Schuler, F., and Coleman, R. E., Aerosol delivery in intubated, mechanically ventilated patients, Crit. Care Med., 13, 81, 1985.
84. Fuller, H. D., Dolovich, M. B., Posmituck, G., Wong, P. W., and Newhouse, M. T., Pressurized aerosol versus jet aerosol delivery to mechanically ventilated patient: comparison of dose to the lungs, Am. Rev. Respir. Dis., 141, 440, 1990.
85. Thomas, S. H. L., O'Doherty, M. J., Page, C. J., Treacher, D. F., and Nunan, T. O., Pulmonary deposition of a nebulized aerosol during mechanical ventilation, Thorax, 48, 154, 1993.
86. Canny, G.J. and Levison, H., Aerosols - therapeutic use and delivery in childhood asthma, Ann. Allergy, 60, 11, 1988.
87. Dolovich, M., Characterization of medical aerosol: physical and clinical requirements for new inhalers, Aerosol Sci. Tech., 22, 392, 1995.
88. Van Oort, M., In vitro testing of dry powder inhalers, Aerosol Sci. Tech., 22, 364, 1995.
89. Borgstrom, L., Bondesson, E., Mren, F., Trofast, E., and Newman, S. P., Lung deposition of budesonide inhaled via Turbohaler: a comparison with terbutaline sulphate in normal subjects, Eur. Respir. J., 7, 69, 1994.
90. Byron, P. R., Aerosol formulation,generation and delivery using metered systems. In Byron, PR (Ed) Respiratory Drug Delivery, CRC Press, Inc., Chapter 7, 1990.
91. Gerrity, T. R., Pathophysiological and disease constraint on aerosol delivery. In Byron, PR (Ed) Respiratory Drug Delivery, CRC Press, Inc., Chapter 1, 1990.
92. Task Group on Lung Dynamics, Health Physics, 12, 173, 1966.
93. Ganderton, D. and Jones, T., Drug Delivery to the Respiratory Tract. Ellis Horwood Series in Biomedicine, Chapter 1, 1988.
94. Dalby, R. N. and Byron, P., Comparison of output particle size distributions from pressurized aerosol formulated as solution or suspension, Pharm. Res., 5, 36, 1988.
95. Hallworth, G. W. and Westmorel, D. G., The twin impringe: a simple device for assessing the delivery of drugs from metered dose pressurized aerosol inhalers, J. Pharm. Pharmacol., 39, 966, 1987.
96. Ferron, G. A., Aerosol particle growth in the human airways using calculated humidity prodies, J. Aerosol Sci., 14, 196, 1983.
97. Scherer, P. W., Haselton, F. R., Hanna, L. M., and Stone, D. R., Growth of hygroscopic aerosols in a model of bronchial airways, J. Appl. Physiol., 47, 544, 1979.
98. Gebhart, J., Anselm, A., Ferron, G., Heyder, J., and Stahlhofen, W., Experimental data on total deposition of hygroscopic particles in the human respiratory tract. In: Masuda, S and Takahashi, K (Eds), Aerosols, Science, Industry, Health and Environment, Pergamon Press, Oxford, 1299, 1990.
99. Anselm, A., Heibel, T., Gebhart, J., and Ferron, G., "In vivo" studies of growth factors of sodium chloride particles in the human respiratory tract, J. Aerosol Sci., 22, 8427, 1991.
100. Chan, H. K., Gonda, I., Development of a systemic theory of suspension inhalation aerosols. II: Aggregates of monodisperse particles nebulized in polydisperse droplets, Int. J. Pharm., 41, 147, 1988.
101. Chan, H. K., Phipps, P. R., Gonda, I., Cook, P., Fulton, R., Young, I., and Bautovich, G., Regional deposition of nebulized hypodense nonisotonic solutions in the human respiratory tract, Eur. Respir., J., 7, 1484, 1994.
102. Parvia, D., Thomson, M. L., Clarke, S. W., and Shannon, H. S., Effect of lung function and mode of inhalation on penetration of aerosol into the human lung, Thorax, 32, 194, 1977.
103. Palmes, E. D., Wang, C., Goldring, R. M., and Altshuler. B., Effect on depth of inhalation of aerosol persistence during breath holding, J. Appl. Physiol. 34, 356, 1973.
104. Newhouse, M. and Ruffin, R., Deposition and fate of aerosolized drugs, Chest, 78 (suppl), 936, 1978.
105. Elliot, R.B., Edgar, B.W., Pilcher, C.C., Questad, C., and McMaster, J., Parenteralabsorption of insulin from the lung in diabetic children, Aust. Paediatr., J., 23, 293, 1987.
106. Köhler, D., Schluter, K.J., Kerp, L., and Matthys, H., Nicht radioaktives verfahren zur messung der lungen permeabilität: inhalation von insulin, Atemw. Lungenkrkh., 13, 230, 1987.
107. Colthorpe, P., Farr, S. J., Tayler, G., Smith, I. J., and Wyatt, D., The pharmacokinetics of pulmonary-delivered insulin: a comparison of intratracheal and aerosol administration to the rabbit, Pharm. Res., 9, 764, 1992.
108. Okumura, K., Iwakawa, S., Yoshida, T., Seki, T., and Komada, F., Intratracheal delivery of insulin absorption from solution and aerosol by rat lung, Int. J. Pharm., 88, 63, 1992.
109. Lurbe, B. L., Georgopoulos, A., and Adams III, G. K., Preliminary study of the efficacy of insulin aerosol delivered by oral inhalation in diabetic patients, JAMA, 269, 2109, 1993.
110. Okada, H., Yamazaki, I., Ogawa, Y., Hirai, S., Yashiki, T., and Mima, T., Vaginal absorption of a potent leuteinizing hormone-releasing hormone analog (leuprolide) in rats: Absorption by various routes and absorption enhancement, J. Pharm. Sci., 71, 1367, 1982.
111. Adjei, A., Johnson, E., Doyle, R., and Sims, K., Formulations of a nanopeptide: in vitro and in vivo studies, J. Pharm. Sci., 76, PS47, 1987.
112. Adjei, A. and Garren, J., Pulmonary delivery of peptide drugs: effect of particle size on bioavailability of leuprolide acetate in healthy male volunteers, Pharm. Res., 7, 565, 1990.
113. Adjei, A., Sundberg, D., Miller, J., and Chun, A., Bioavailability of leuprolide acetate following nasal and inhalation delivery to healthy humans, Pharm. Res., 9, 244, 1992.
114. Adjei, A., Doyle, R., Johnson, E., Pratt, M., and Finley, R., Bioavailability of leuprolide following intratracheal administration to beagle dogs, Int. J. Pharm., 61, 135, 1990.
115. Adjei, A., Hui, J., Finley, R., Lin, T., Lancaster, J., and Fort, F, Pulmonary bioavailability of leuprolide acetate following multiple dosing to beagle dogs: some pharmacokinetic and preclinical issues, Int. J. Pharm., 107, 57, 1994.
116. Bennett, D. B., Tyson, E., Nerenberg, C. A., Mah, S., deGroot, J. S., and Teitelbaum, Z., Pulmonary delivery of detirelix by intratracheal instillation and aerosol inhalation in the briefly anesthetized dog, Pharm. Res., 11, 1048, 1994.
117. Powell, M. F., Sanders, L. M., Rogerson, A., and Si, V., Parenteral peptide formulation: Chemical and physical properties of native leuteinizing hormone-releasing hormone (LHRH) and hydrophobic analogues in aqueous solution, Pharm. Res., 8, 1258, 1991.
118. Pontiroli, A., Alberto, M., and Pozza, G., Intranasal calcitonin and plasma calcium concentrations in normal subjects, Br. Med. J., 290, 1390, 1985.
119. 1,7)-eel calcitonin by various protease inhibitors in rats, Pharm. Res., 11, 909, 1994.
120. Kobayashi, S., Kondo, S., and Juni, K., Study on pulmonary delivery of salmon calcitonin in rats: effect of protease inhibitors and absorption enhancers, Pharm. Res., 11, 1239, 1994.
121. Patton, J. S., McCabe, J. G., Hansen, S. E., and Daugherty, A. L., Absorption of human growth hormone from the rat lung, Biotech. Ther., 1, 213, 1990.
122. Patton, J. S. and Platz, R. M., Routes of delivery: Case studies. (2) Pulmonary delivery of peptides and proteins for systemic action, Adv. Drug Del. Rev., 8, 179, 1992.
123. Patton, J. S. and Platz, R. M., Systemic delivery of peptides and proteins through the pulmonary route, J. Aer. Med., 6 (suppl), 53, 1993.
124. 1-antitrypsin: use of the epithelial surface of the lower respiratory tract to administer proteins of therapeutic importance, Proc. Natl. Acad. Sci. USA, 86, 680, 1989.
125. Platz, R. M., Winters, M. A., and Pitt, C. G., Pulmonary administration of granulocyte colony stimulating factors, International publication number WO 92/16192, (1992).
126. Nelson, S., Bagby, G., Andresen, J., Shellito, J., and Summer, W., Intratracheal granulocyte colony stimulating factor enhances systemic and pulmonary host defenses. Am. Rev. Respir. Dis., 143, S398, 1991.
127. Demetri, G. D. and Griffin, J. D., Granulocyte-stimulating factor and its receptor, J. Am. Soc. Hematol., 78, 2791, 1991.
128. Niven, R. W., Lott, F. D., and Cribbs, J. M., Pulmonary absorption of recombinant methionyl human granulocyte colony stimulating factor (rhG-CSF) after intratracheal instillation to the hamster, Pharm. Res., 10, 1604, 1993.
129. Niven, R. W., Lott, F. D., Ip, A. Y., and Cribbs, J. M., Pulmonary delivery of powders and solutions containing recombinant human granulocyte colony stimulating factor (rhG-CSF) to the rabbit, Pharm. Res., 11, 1101, 1994.
130. Niven, R.W., Whitcomb, K.L., Shaner, L., Ralph, L.D., Habberfield, A.D., and Wilson, J. V. Pulmonary absorption of polyethylene glycolated recombinant human granulocyte colony stimulating factor (PEG-rhG-CSF), J. Contrl. Rel., 32, 177, 1994.
131. 99mTechnetium as a marker of liposomal deposition and clearance in the human lung, Int. J. Pharm., 26, 303, 1985.
132. Fielding, R. M. and Abra, R. M., Factors affecting the release of terbutaline from liposome formulations after intratracheal instillation in the guinea pig, Pharm. Res., 9, 220, 1992.
133. Jurima-Romet, M., Barber, R. F., Demeester, J., and Shek, P. N., Distribution studies of liposome-encapsulated glutathione administered to the lung, Int. J. Pharm., 63, 227, 1990.
134. Poyner, E. A., Alpar, H. O., Almeida, A. J., Gamble, M. D., and Brown, M. R. W., A comparative study on the pulmonary delivery of tobramycin encapsulated into liposomes and PLA microspheres following intravenous and endotracheal delivery, J. Contrl. Rel., 35, 41, 1995.
135. 99mtechnetium-labelled beclomethasone dipropionate dilauroylphosphatidyl-choline liposome aerosol in normal volunteers, Int. J. Pharm. 115, 209, 1995.
136. Liu, F. Y., Shao, Z., Kildsig, D. O., and Mitra, A. K., Pulmonary delivery of free and liposomal insulin, Pharm. Res., 10, 228, 1993.
137. Brange, J., Ribel, U., Hansen, J. F., and Volund, A., The association state of insulin determines the rate of absorption of regular insulin, Diabetes, 37 (Suppl. 1), 163 A, 1988.
138. Pillai, R. S., Yeates, D. B., Miller, I. F., and Hickey, A. J., Controlled release from condensation coated respirable aerosol particles, J. Aerosol Sci., 25, 461, 1994.
139. Yamamoto, A., Umomori, S., and Muranishi, S., Absorption enhancement of intrapulmonary administered insulin by various absorption enhancers and protease inhibitors in rats, J. Pharm. Pharmacol., 46, 14, 1993.
140. Raehs, S. C., Sandow, J., Wirth, K., and Merkle, H. P., The adjuvent effect of bacitracin on nasal absorption of gonadorelin and buserelin in rat, Pharm. Res., 5, 689, 1988.
141. Saffran, M., Bedra, C., Kumar, S., and Neckers, D.C., Vasopressin: a model for the study of effects of additives on the oral and rectal administration of peptide drugs, J. Pharm. Sci., 77, 33, 1988.
142. Enna, S.J. and Schanker, L. S., Absorption of saccharides and urea from the rat lung, Am. J. Physiol., 222, 409, 1972.
143. 2-EDTA, and aprotinin on rectal, nasal, and buccal insulin delivery, Pharm. Res., 5, 305, 1988.
144. Morita, T., Yamamoto, A., Itashida, M., and Sezaki, H., Effect of various absoqition promoters on pulmonary absorption of drugs with different molecular weight, Biol. Pharm. Bull., 16, 259, 1993.
145. Patton, J. S., Trinchero, P., and Platz, R. M., Bioavailability of pulmonary delivered peptides and proteins: a-interferon, calcitonins and parathyroid hormones, J. Contrl. Rel., 28, 79, 1994.
146. Yamahara, H., Morimoto, K., Lee, V. H. L., and Kim, K., Effects of protease inhibitors on vasopressin transport across rat alveolar epithelial cell monolayers, Pharm. Res., 11, 1617, 1994.
147. Yamahara, H., Lee, V. H. L., and Kim, K., Fate of insulin during transit across rat alveolar epithelial cell monolayers, Eur. J. Biopharm., 40, 294, 1994b.
148. Kobayashi, S., Kondo, S., and Juni, K., Permeability of peptides and proteins in human cultured alveolar A549 cell monolayer, Pharm. Res., 12, 115, 1995.
149. Williams, M. C., Endocytosis in alveolar type II cells: effect of charge and size of tracers, Proc. Natl Acad. Sci. USA, 81, 6054, 1984.
150. Lansley, A. B., Mucociliary clearance and drug delivery via the respiratory tract, Adv. Drug Del. Rev., 11, 229, 1993.
151. Wang, L.Y., Toledo-Velasquez, D., Schwegler-Berry, D., Ma, J.K.H., and Rojanasakul, Y. (1993) Transport and hydrolysis of enkephalins in cultured alveolar epithelial monolayers, Pharm. Res., 10, 1662, 1993.
152. Wang, L. Y., Ma, J. K. H., Pan, W. R, Toledo-Velasquez, D., Malanga, C. J., and Rojanasakul, Y., Alveolar permeability enhancement by oleic acid and related fatty acids: evidence for a calcium-dependent mechanism, Pharm. Res., 11, 513, 1994.