Skip to main content
SpringerLink
Log in
SpringerLink
Log in

In Vivo Animal Models for Controlled-Release Pulmonary Drug Delivery

  • Chapter
  • First Online:
Controlled Pulmonary Drug Delivery

Part of the book series: Advances in Delivery Science and Technology ((ADST))

Abstract

Prediction of drug delivery performance in the human lung is most often based on observations in commonly used laboratory animals. Even though cell cultures are a useful and inexpensive tool, they are limited to the study of single or a few processes. The complexity and numerous biological interactions of a drug and delivery system can be accurately evaluated only in vivo. The anatomical and physiological differences between species should be carefully considered and are reviewed in this chapter. In addition, the methods of aerosol delivery and dose calculation are presented. Then, techniques and methods to assess drug delivery performance in these in vivo models are reviewed. Lastly, animal models of disease are discussed. These factors are crucial for the correct interpretation of the results of studies and the subsequent extrapolation to humans.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Patton JS, Fishburn CS, Weers JG (2004) The lungs as a portal of entry for systemic drug delivery. Proc Am Thorac Soc 1(4):338–344

    Article  PubMed  CAS  Google Scholar 

  2. Schanker LS (1978) Drug absorption from the lung. Biochem Pharmacol 27(4):381–385

    Article  PubMed  CAS  Google Scholar 

  3. Edwards DA et al (1997) Large porous particles for pulmonary drug delivery. Science 276(5320):1868–1871

    Article  PubMed  CAS  Google Scholar 

  4. Gonda I (1992) Targeting by deposition. In: Hickey AJ (ed) Pharmaceutical inhalation aerosol technology. Marcel Dekker, New York, pp 61–82

    Google Scholar 

  5. Suarez S, Hickey AJ (2000) Drug properties affecting aerosol behavior. Respir Care 45(6):652–666

    PubMed  CAS  Google Scholar 

  6. Gehr P et al (1993) Surfactant and inhaled particles in the conducting airways: structural, stereological, and biophysical aspects. Microsc Res Technol 26(6):423–436

    Article  CAS  Google Scholar 

  7. Beck BD, Brain JD, Bohannon DE (1982) An in vivo hamster bioassay to assess the toxicities of particulates for the lungs. Toxicol Appl Pharmacol 66(1):9–29

    Article  PubMed  CAS  Google Scholar 

  8. Oberdorster G, Cox C, Gelein R (1997) Intratracheal instillation versus intratracheal inhalation of tracer particles for measuring lung clearance function. Exp Lung Res 23(1):17–34

    Article  PubMed  CAS  Google Scholar 

  9. Niven RW (1992) Modulated drug therapy with inhalation aerosols. In: Hickey AJ (ed) Pharmaceutical inhalation aerosol technology. Marcel Dekker, New York, pp 321–359

    Google Scholar 

  10. Florea BI et al (2003) Drug transport and metabolism characteristics of the human airway epithelial cell line Calu-3. J Control Release 87:131–138

    Article  PubMed  CAS  Google Scholar 

  11. Gumbleton M et al (2003) Targeting caveolae for vesicular drug transport. J Control Release 87:139–151

    Article  PubMed  CAS  Google Scholar 

  12. Kim K-J, Borok Z, Crandall ED (2001) A useful in vitro model for transport studies of alveolar epithelial barrier. Pharm Res 18(3):253–255

    Article  PubMed  CAS  Google Scholar 

  13. Kim K-J, Malik AB (2003) Protein transport across the lung epithelial barrier. Am J Physiol 284(2):L247–L259

    CAS  Google Scholar 

  14. Patton JS (1996) Mechanisms of macromolecule absorption by the lungs. Adv Drug Deliv Rev 19:3–36

    Article  CAS  Google Scholar 

  15. Forbes B, Ehrhardt C (2005) Human respiratory epithelial cell culture for drug delivery applications. Eur J Pharm Biopharm 60(2):193–205

    Article  PubMed  CAS  Google Scholar 

  16. Hsu MC-P, Bai JPF (1998) Investigation into the presence of insulin-degrading enzyme in culture type II alveolar cells and the effects of enzyme inhibitors on pulmonary bioavailability of insulin in rats. J Pharm Pharmacol 50:507–514

    Article  PubMed  CAS  Google Scholar 

  17. Sakagami M (2004) Insulin disposition in the lung following oral inhalation in humans: a meta-analysis of its pharmacokinetics. Clin Pharmacokinet 43(8):539–552

    Article  PubMed  CAS  Google Scholar 

  18. 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

    Article  PubMed  CAS  Google Scholar 

  19. 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

    Article  PubMed  CAS  Google Scholar 

  20. Fernandes CA, Vanbever R (2009) Preclinical models for pulmonary drug delivery. Expert Opin Drug Deliv 6(11):1231–1245

    Article  PubMed  CAS  Google Scholar 

  21. Brown LK (1986) Static lung volumes: functional residual capacity, residual volume and total lung capacity. In: Miller AL (ed) Pulmonary function tests in clinical and occupational lung disease. Grune and Stratton, Orlando, pp 77–114

    Google Scholar 

  22. Chaffee VW (1974) Surgery of laboratory animals. In: Melby EC Jr, Altman NH (eds) Handbook of laboratory animal science. CRC Press, Cleveland, pp 233–273

    Google Scholar 

  23. Sheldon RL (2000) Pulmonary function testing. In: Wilkins RL, Krider SJ, Sheldon RL (eds) Clinical assessment in respiratory care. Mosby, St. Louis, pp 144–155

    Google Scholar 

  24. Hickey A, Garcia-Contreras L (2001) Immunological and toxicological implications for short-term studies in animals of pharmaceutical aerosol delivery to the lungs: relevance to humans. Crit Rev Ther Drug Carrier Syst 18(4):387–431

    PubMed  CAS  Google Scholar 

  25. Phalen RF, Oldham MJ (1983) Airway structures: tracheobronchial airway structure as revealed by casting techniques. Am Rev Respir Dis 128(2):s1–s4

    PubMed  CAS  Google Scholar 

  26. Esch J, Spektor D, Lippmann M (1988) Effect of lung airway branching pattern and gas composition on particle deposition. II. Experimental studies in human and canine lungs. Exp Lung Res 14(3):321–348

    Article  PubMed  CAS  Google Scholar 

  27. Spektor DM et al (1985) Influence of airway and airspace sizes on particle deposition in excised donkey lungs. Exp Lung Res 9(3–4):363–387

    Article  PubMed  CAS  Google Scholar 

  28. Yeh H, Phalen R, Raabe O (1976) Factors influencing the deposition of inhaled particles. Environ Health Perspect 15:147–156

    Article  PubMed  CAS  Google Scholar 

  29. Lippmann M, Schlesinger RB (1984) Interspecies comparisons of particle deposition and mucociliary clearance in tracheobronchial airways. J Toxicol Environ Health 13(2–3):441–469

    Article  PubMed  CAS  Google Scholar 

  30. Staufer D (1975) Scaling theory for aerosol deposition in the lungs of different mammals. J Aerosol Sci 6:223–225

    Article  Google Scholar 

  31. McMahon T, Brain J, LeMott S (1977) Species difference in aerosol deposition. In: Walton W (ed) Inhaled particles. Pergamon Press, Oxford, pp 23–33

    Google Scholar 

  32. Tyler WS (1983) Small airways and terminal units: comparative subgross anatomy of lungs. Am Rev Respir Dis 128(2):s32–s36

    PubMed  CAS  Google Scholar 

  33. Crapo JD et al (1983) Morphometric characteristics of cells in the alveolar region of mammalian lungs. Am Rev Respir Dis 128(2):s43–s46

    Google Scholar 

  34. Bowden DH (1983) Cell turnover in the lung. Am Rev Respir Dis 128(2):s46–s48

    PubMed  CAS  Google Scholar 

  35. Krombach F et al (1997) Cell size of alveolar macrophages: an interspecies comparison. Environ Health Perspect 105(Suppl 5):1261–1263

    Article  PubMed  Google Scholar 

  36. Matulionis DH (1984) Effects of cigarette smoke generated by different smoking machines on pulmonary macrophages of mice and rats. J Anal Toxicol 8(4):187–191

    PubMed  CAS  Google Scholar 

  37. Oosting RS et al (1991) Species differences in impairment and recovery of alveolar macrophage functions following single and repeated ozone exposures. Toxicol Appl Pharmacol 110(1):170–178

    Article  PubMed  CAS  Google Scholar 

  38. Schlesinger RB, Fine JM, Chen LC (1992) Interspecies differences in the phagocytic activity of pulmonary macrophages subjected to acidic challenge. Fundam Appl Toxicol 19(4):584–589

    Article  PubMed  CAS  Google Scholar 

  39. Brain JD, Mensah GA (1983) Comparative toxicology of the respiratory tract. Am Rev Respir Dis 128(2):s87–s90

    PubMed  CAS  Google Scholar 

  40. Nguyen B et al (1982) Differences in phagocytosis and killing by alveolar macrophages from humans, rabbits, rats and hamsters. Infect Immun 36:504–509

    PubMed  CAS  Google Scholar 

  41. Huber G, Johanson W, LaForce F (1977) Experimental models and pulmonary antimicrobial defenses. In: Brain J, Proctor D, Reid L (eds) Respiratory defense mechanisms. Marcel Dekker, New York, pp 983–1001

    Google Scholar 

  42. Spicer SS, Schulte BA, Thomopoulos GN (1983) Histochemical properties of the respiratory tract epithelium in different species. Am Rev Resp Dis 128(2):s20–s26

    PubMed  CAS  Google Scholar 

  43. Plopper CG (1983) Comparative morphologic features of bronchiolar epithelial cells: the Clara cell. Am Rev Resp Dis 128(2):s37–s41

    PubMed  CAS  Google Scholar 

  44. Dvorak AM, Dvorak HF, Galli SJ (1983) Ultrastructural criteria for identification of mast cells and basophils in humans, guinea pigs and mice. Am Rev Resp Dis 128(2):s49–s52

    PubMed  CAS  Google Scholar 

  45. Dvorak AM et al (1980) Crohn’s disease: transmission electron microscopic studies II. Immunologic inflammatory response. Alterations of mast cells, basophils, eosinophils, and the microvasculature. Hum Pathol 11:606–619

    Article  PubMed  CAS  Google Scholar 

  46. Kay M (1983) Pulmonary vasculature and nerves: comparative morphologic features of the pulmonary vasculature in mammals. Am Rev Resp Dis 128(2):s53–s57

    PubMed  CAS  Google Scholar 

  47. Leak LV, Jamuar MP (1983) Ultrastructure of pulmonary lymphatic vessels. Am Rev Resp Dis 128(2):s59–s65

    PubMed  CAS  Google Scholar 

  48. Schneeberger EE (1978) Structural basis for some permeability properties of the air–blood barrier. Fed Proc 37(11):2471–2478

    PubMed  CAS  Google Scholar 

  49. Sayani AP, Chien YW (1996) Systemic delivery of peptides and proteins across absorptive mucosae. Crit Rev Ther Drug Carrier Syst 13(1–2):85–184

    PubMed  CAS  Google Scholar 

  50. Devereux TR, Domin BA, Philpot RM (1989) Xenobiotic metabolism by isolated pulmonary cells. Pharmacol Ther 41(1–2):243–256

    Article  PubMed  CAS  Google Scholar 

  51. Zhang JY, Wang Y, Prakash C (2006) Xenobiotic-metabolizing enzymes in human lung. Curr Drug Metab 7(8):939–948

    Article  PubMed  CAS  Google Scholar 

  52. Schanker L, Mitchel E, Brown R (1986) Species comparison of drug absorption from the lung after inhalation or intratracheal injection. Drug Metab Dispos 14:79–88

    PubMed  CAS  Google Scholar 

  53. Hill NS, O’Brien RF, Rounds S (1984) Repeated lung injury due to alpha-naphthylthiourea causes right ventricular hypertrophy in rats. J Appl Physiol 56(2):388–396

    PubMed  CAS  Google Scholar 

  54. Smith PC, Heath D (1976) Paraquat. Biochem Pharmacol 25:411–445

    Google Scholar 

  55. Snipes MB (1989) Long-term retention and clearance of particles inhaled by mammalian species. Crit Rev Toxicol 20(3):175–211

    Article  PubMed  CAS  Google Scholar 

  56. Dorato MA (1990) Overview of inhalation toxicology. Environ Health Perspect 85:163–170

    Article  PubMed  CAS  Google Scholar 

  57. Raeburn D, Underwood SL, Villamil ME (1992) Techniques for drug delivery to the airways, and the assessment of lung function in animal models. J Pharmacol Toxicol Meth 27:143–159

    Article  CAS  Google Scholar 

  58. Byron PR, Clark AR (1985) Drug absorption from inhalation aerosols administered by positive-pressure ventilation. I: administration of a characterized, solid disodium fluorescein aerosol under a controlled respiratory regime to the beagle dog. J Pharm Sci 74(9):934–938

    Article  PubMed  CAS  Google Scholar 

  59. Garcia-Contreras L et al (2007) Inhaled capreomycin large porous particles for the treatment of tuberculosis in the guinea pig model. Antimicrob Agents Chemother 51(8):2830–2836

    Article  PubMed  CAS  Google Scholar 

  60. Garcia-Contreras L et al (2010) Dry powder PA-824 aerosols for the treatment of tuberculosis in guinea pigs. Antimicrob Agents Chemother 54(4):1436–1442

    Article  PubMed  CAS  Google Scholar 

  61. Asplund PT et al (1996) Longitudinal distribution of ozone absorption in the lung: effect of continuous inhalation exposure. Arch Environ Health 51(6):431–438

    Article  PubMed  CAS  Google Scholar 

  62. García-Contreras L, Hickey AJ (2002) Pharmacokinetics of aerosolized rifampicin in the guinea pig. In: Dalby RN et al (eds) Respiratory drug delivery VIII. Davis Horwood International Publishing, Raleigh

    Google Scholar 

  63. García-Contreras L et al (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

    Article  PubMed  Google Scholar 

  64. Alexander DJ et al (2008) Association of Inhalation Toxicologists (AIT) Working party recommendation for standard delivered dose calculation and expression in non-clinical aerosol inhalation toxicology studies with pharmaceuticals. Inhal Toxicol 20(13):1179–1189

    Article  PubMed  CAS  Google Scholar 

  65. Garcia-Contreras L et al (2006) Pharmacokinetics of aerosolized rifampicin large porous particles in the guinea pig. In: Dalby RN et al (eds) Respiratory drug delivery X. Davis Healthcare International Publishing, River Grove, pp 873–876

    Google Scholar 

  66. Suarez S et al (2001) Airways delivery of rifampicin microparticles for the treatment of tuberculosis. J Antimicrob Chemother 48:431–434

    Article  PubMed  CAS  Google Scholar 

  67. Suarez S et al (2001) Respirable PLGA microspheres containing rifampicin for the treatment of tuberculosis: screening in an infectious disease model. Pharm Res 19:1315–1319

    Article  Google Scholar 

  68. Kuraki T et al (2000) Human neutrophile elastase using microsprayer induced emphysematous changes in rats. Am J Respir Crit Care Med 161(2):872

    Google Scholar 

  69. Kuraki T et al (2002) A novel oral neutrophia elastase inhibitor (ONO-6818) inhibits human neutrophil elastase-induced emphysema in rats. Am J Respir Crit Care Med 166:496–500

    Article  PubMed  Google Scholar 

  70. Mata J et al (2007) Evaluation of emphysema severity and progression in a rabbit model: a comparison of hyperpolarized He-3 and Xe-129 diffusion MRI with lung morphometry. J Appl Physiol 102:1273–1280

    Article  PubMed  Google Scholar 

  71. Taylor M, Hickey A, VanOort M (2007) Manufacture, characterization, and pharmacodynamic evaluation of engineered ipratropium bromide particles. Pharm Dev Technol 11:321–336

    Article  CAS  Google Scholar 

  72. Gagnadoux F et al (2005) Safety of pulmonary administration of gemcitabine in rats. J Aerosol Med 18(2):198–206

    Article  PubMed  CAS  Google Scholar 

  73. Gagnadoux F et al (2005) Aerosol delivery of chemotherapy in an orthotopic model of lung cancer. Eur Respir J 26:657–661

    Article  PubMed  CAS  Google Scholar 

  74. Beck SE et al (2002) Deposition and expression of aerosolized rAAV vectors in the lungs of Rhesus macaques. Mol Ther 6:546–554

    Article  PubMed  CAS  Google Scholar 

  75. Flotte TR, Laube BL (2001) Gene therapy in cystic fibrosis. Chest 120:124S–131S

    Article  PubMed  CAS  Google Scholar 

  76. Takeda K et al (2003) Surfactant protein D regulates airway function and allergic inflammation through modulation of macrophage function. Am J Respir Crit Care Med 168:783–789

    Article  PubMed  Google Scholar 

  77. Garcia-Contreras L et al (2003) Evaluation of novel calcium phosphate particles as pulmonary delivery systems for insulin in rats. AAPSPharmSci 3(3):9

    Google Scholar 

  78. Garcia-Contreras L et al (2001) Immediate and short-term cellular and biochemical responses to pulmonary single-dose studies of insulin and H-MAP. Pharm Res 18(12):1685–1693

    Article  PubMed  CAS  Google Scholar 

  79. Suarez S et al (2001) Facilitation of pulmonary insulin absorption by H-MAP: pharmacokinetics and pharmacodynamics in rats. Pharm Res 18(12):1677–1684

    Article  PubMed  CAS  Google Scholar 

  80. Huang J et al (2003) A novel dry powder influenza vaccine and intranasal delivery technology: induction of systemic and mucosal immune responses in rats. Vaccine 23:794–801

    Article  CAS  Google Scholar 

  81. Lu D et al (2007) Poly (lactide-co-glycolide) microspheres in respirable sizes enhance an in vitro T cell response to recombinant mycobacterium tuberculosis antigen 85B. Pharm Res 24(10):1834–1843

    Article  PubMed  CAS  Google Scholar 

  82. Codrons V et al (2004) Impact of formulation and methods of pulmonary delivery on absorption of parathyroid hormone from rat lungs. J Pharm Sci 93(5):1241–1252

    Article  PubMed  CAS  Google Scholar 

  83. Gervelas C et al (2007) Direct lung delivery of a dry powder formulation of DTPA with improved aerosolization properties: effect on lung and systemic decorporation of plutonium. J Control Release 118(1):78–86

    Article  PubMed  CAS  Google Scholar 

  84. Grainger CI et al (2003) Administration of an insulin powder to the lungs of cynomolgus monkeys using a Penn Century insufflator. Int J Pharm 269:523–527

    Article  CAS  Google Scholar 

  85. Koushik K et al (2004) Pulmonary delivery of deslorelin: large-porous PLGA particles and HPβCD complexes. Pharm Res 21(7):1119–1126

    Article  PubMed  CAS  Google Scholar 

  86. Minne A, Vanbever R (2007) Development of an inhalation dry powder and assessment of its pulmonary distribution in mice. J Aerosol Med 20(2):164–209

    Article  Google Scholar 

  87. Tetsuya O, Hiroaki O (2006) Nanoparticle-containing microspheres drug delivery system (DDS) for inhalation therapy. J Aerosol Res 21(1):10–15

    Google Scholar 

  88. Burnell PKP et al (2006) Powder deposition in rats assessed in vivo and in silico. In: Dalby RN et al (eds) Respiratory drug delivery X. Davis Healthcare International Publishing, River Grove, pp 625–627

    Google Scholar 

  89. Suarez S, Talton JD, Hochhaus G (1998) Assessment of pulmonary selectivity of triamcinolone acetonide powders using an ex vivo receptor binding assay. In: Dalby RN, Byron PR, Farr SJ (eds) Respiratory drug delivery VI. Interpharm Press, Buffalo Grove, p 425

    Google Scholar 

  90. Newman SP, Wilding IR (1998) Gamma scintigraphy: in vivo technique for assessing the equivalence of inhaled products. Int J Pharm 170:1–9

    Article  CAS  Google Scholar 

  91. Dolovich MB (2001) Measuring total and regional lung deposition using inhaled radiotracers. J Aerosol Med 14(Suppl 1):S35–S44

    Article  PubMed  CAS  Google Scholar 

  92. Batrakova EV et al (2010) Effects of pluronic and doxorubicin on drug uptake, cellular metabolism, apoptosis and tumor inhibition in animal models of MDR cancers. J Control Release 143:290–301

    Article  PubMed  CAS  Google Scholar 

  93. Deshpande DS et al (2005) Gamma scintigraphic evaluation of a miniaturized AERx pulmonary delivery system for aerosol delivery to anesthetized animals using a positive pressure ventilation system. J Aerosol Med 18(1):34–44

    Article  PubMed  CAS  Google Scholar 

  94. Deuse T et al (2010) Mechanisms behind local immunosuppression using inhaled tacrolimus in preclinical models of lung transplantation. Am J Respir Cell Mol Biol 43:403–412

    Article  PubMed  CAS  Google Scholar 

  95. Gagnadoux F et al (2006) Gemcitabine aerosol: in vitro antitumor activity and deposition imaging for preclinical safety assessment in baboons. Cancer Chemother Pharmacol 58(2):237–244

    Article  PubMed  CAS  Google Scholar 

  96. Khanna C et al (1997) Nebulized interleukin 2 liposomes: aerosol characteristics and biodistribution. J Pharm Pharmacol 49(10):960–971

    Article  PubMed  CAS  Google Scholar 

  97. Kreyling WG et al (1999) Anatomic localization of 24- and 96-h particle retention in canine airways. J Appl Physiol 87(1):269–284

    PubMed  CAS  Google Scholar 

  98. Richter T et al (2010) Effects of posture on regional pulmonary blood flow in rats as measured by PET. J Appl Physiol 108(2):422–429

    Article  PubMed  Google Scholar 

  99. Young BC et al (2007) Toxic pneumonitis caused by inhalation of hydrocarbon waterproofing spray in two dogs. J Am Vet Med Assoc 23(1):74–78

    Article  Google Scholar 

  100. Linder J, Rennard SI (1988) Bronchoalveolar lavage. ASCP Press, Chicago, p 179

    Google Scholar 

  101. Mauderly JL (1977) Bronchopulmonary lavage of small laboratory animals. Lab Anim Sci 27:255–261

    PubMed  CAS  Google Scholar 

  102. Kipnis E (2005) Using urea as an endogenous marker of bronchoalveolar lavage dilution. Crit Care Med 33(9):2153

    Article  PubMed  Google Scholar 

  103. Harkness J, Wagner JE (1995) The biology and medicine of rabbits and rodents. Williams & Wilkins, Philadelphia

    Google Scholar 

  104. Oliver CE et al (2007) Pharmacokinetics of ruminally dosed sodium [36Cl]chlorate in beef cattle. J Vet Pharmacol Ther 30(4):358–365

    Article  PubMed  CAS  Google Scholar 

  105. Olsen L et al (2007) Cetirizine in horses: pharmacokinetics and effect of ivermectin pretreatment. J Vet Pharmacol Ther 30(3):194–200

    Article  PubMed  CAS  Google Scholar 

  106. Borges FA et al (2007) Pharmacokinetics of a new long acting endectocide formulation containing 2.25% ivermectin and 1.25% abamectin in cattle. J Vet Pharmacol Ther 30(1):62–67

    Article  PubMed  CAS  Google Scholar 

  107. Hubenov H et al (2007) Pharmacokinetic studies on tobramycin in horses. J Vet Pharmacol Ther 30(4):353–357

    Article  PubMed  CAS  Google Scholar 

  108. Marín P et al (2007) Pharmacokinetics after intravenous, intramuscular and subcutaneous administration of difloxacin in sheep. Res Vet Sci 83(2):234–238

    Article  PubMed  CAS  Google Scholar 

  109. Shukla M et al (2007) Comparative plasma pharmacokinetics of meloxicam in sheep and goats following intravenous administration. Comp Biochem Physiol C Toxicol Pharmacol 145(4):528–532

    Article  PubMed  CAS  Google Scholar 

  110. Suarez S, Hickey AJ (2001) Pharmacokinetic and pharmacodynamic aspects of inhaled therapeutic agents. In: Martonen T (ed) Medical applications of computer modelling: the respiratory system. WIT Press, Southampton, pp 225–304

    Google Scholar 

  111. Chandra T, Miller IF, Yeates DB (1992) A pore transport model for pulmonary alveolar epithelium. Ann Biomed Eng 20:481–494

    Article  PubMed  CAS  Google Scholar 

  112. Clark AR, Egan M (1994) Modelling the deposition of inhaled powder drug aerosols. J Aerosol Sci 25:175–186

    Article  Google Scholar 

  113. Gibaldi M, Perrier D (1982) Pharmacokinetics. Marcel Dekker, New York

    Google Scholar 

  114. Adjei A, Qiu Y, Gupta P (1996) Bioavailability and pharmacokinetics of inhaled drugs. In: Hickey AJ (ed) Inhalation aerosols. physical and biological basis for therapy. Marcel Dekker, New York, pp 197–232

    Google Scholar 

  115. Gabrielsson J, Weiner D (2000) Pharmacokinetic and pharmacokinetic data analysis: concepts and applications. Swedish Pharmaceutical Press, Stockholm

    Google Scholar 

  116. Chiu WA et al (2007) Evaluation of physiologically based pharmacokinetic models for use in risk assessment. J Appl Toxicol 27(3):218–237

    Article  PubMed  CAS  Google Scholar 

  117. Krishnan K, Johanson G (2005) Physiologically-based pharmacokinetic and toxicokinetic models in cancer risk assessment. J Environ Sci Health C Environ Carcinog Ecotoxicol Rev 23(1):31–53

    PubMed  Google Scholar 

  118. Byron PR (1986) Prediction of drug residence times in regions of the human respiratory tract following aerosol inhalation. J Pharm Sci 75(5):433–438

    Article  PubMed  CAS  Google Scholar 

  119. Gonda I (1988) Drugs administered directly into the respiratory tract: modeling of the duration of effective drug levels. J Pharm Sci 77(4):340–346

    Article  PubMed  CAS  Google Scholar 

  120. Chowhan Z, Amaro A (1976) Pulmonary absorption studies utilizing in situ rat lung model: designing dosage regimen for bronchial delivery of new drug entities. J Pharm Sci 65(11):1669–1672

    Article  PubMed  CAS  Google Scholar 

  121. Loo J, Riegelman S (1968) New method for calculatin the intrinsec absorption rate of drugs. J Pharm Sci 57:918–928

    Article  PubMed  CAS  Google Scholar 

  122. Wagner J (1970) “Absorption rate constants” calculated according to one-compartment open model with first-order absorption: implications for the in-vivo in-vitro correlations. J Pharm Sci 59:1049

    Article  PubMed  CAS  Google Scholar 

  123. Le Brun PP et al (1999) Can tobramycin inhalation be improved with a jet nebulizer? Ther Drug Monit 21(6):619

    Google Scholar 

  124. Patton JS, Bukar J, Nagarajan S (1999) Inhaled insulin. Adv Drug Deliv Rev 35:235–247

    Article  PubMed  CAS  Google Scholar 

  125. Niven RW et al (1995) Systemic absorption and activity of recombinant consensus interferon and after intratracheal instillation and aerosol administration. Pharm Res 12:1889–1895

    Article  PubMed  CAS  Google Scholar 

  126. Colthorpe P et al (1992) The pharmacokinetics of pulmonary delivered insulin: a comparison of intratracheal and aerosol administration to the rabbit. Pharm Res 9:764–768

    Article  PubMed  CAS  Google Scholar 

  127. Pillai RS et al (1996) The effect of pulmonary delivered insulin on blood glucose levels using two nebulizers. J Aerosol Med 9:227–240

    Article  PubMed  CAS  Google Scholar 

  128. Jonasson S et al (2009) Comparisons of effects of intravenous and inhaled methacholine on airway physiology in a murine asthma model. Respir Physiol Neurobiol 165(2–3):229–236

    Article  PubMed  CAS  Google Scholar 

  129. Latimer P et al (2009) Aerosol delivery of liposomal formulated paclitaxel and vitamin E analog reduces murine mammary tumor burden and metastases. Exp Biol Med (Maywood) 234(10):1244–1252

    Article  CAS  Google Scholar 

  130. Hwang SK et al (2009) Repeated aerosol delivery of carboxyl-terminal modulator protein suppresses tumor in the lungs of K-rasLA1 mice. Am J Respir Crit Care Med 179(12):1131–1140

    Article  PubMed  CAS  Google Scholar 

  131. Sabet M et al (2009) Efficacy of aerosol MP-376, a levofloxacin inhalation solution, in models of mouse lung infection due to Pseudomonas aeruginosa. Antimicrob Agents Chemother 53(9):3923–3928

    Article  PubMed  CAS  Google Scholar 

  132. Huang YY, Wang CH (2006) Pulmonary delivery of insulin by liposomal carriers. J Control Release 113(1):9–14

    Article  PubMed  CAS  Google Scholar 

  133. Morello M et al (2009) Dry-powder pulmonary insufflation in the mouse for application to vaccine or drug studies. Tuberculosis (Edinb) 89(5):371–377

    Article  CAS  Google Scholar 

  134. Alpar HO et al (2005) Biodegradable mucoadhesive particulates for nasal and pulmonary antigen and DNA delivery. Adv Drug Deliv Rev 57(3):411–430

    Article  PubMed  CAS  Google Scholar 

  135. Wong JP et al (2003) Liposome delivery of ciprofloxacin against intracellular Francisella tularensis infection. J Control Release 92(3):265–273

    Article  PubMed  CAS  Google Scholar 

  136. Seong JH et al (2006) Polyethylenimine-based antisense oligodeoxynucleotides of IL-4 suppress the production of IL-4 in a murine model of airway inflammation. J Gene Med 8(3):314–323

    Article  PubMed  CAS  Google Scholar 

  137. Bakker-Woudenberg IA et al (2002) Ciprofloxacin in polyethylene glycol-coated liposomes: efficacy in rat models of acute or chronic Pseudomonas aeruginosa infection. Antimicrob Agents Chemother 46(8):2575–2581

    Article  PubMed  CAS  Google Scholar 

  138. Amidi M et al (2009) Efficacy of pulmonary insulin delivery in diabetic rats: use of a model-based approach in the evaluation of insulin powder formulations. J Control Release 135(1):25–34

    Article  CAS  Google Scholar 

  139. Ungaro F et al (2008) Insulin-loaded PLGA/cyclodextrin large porous particles with improved aerosolization properties: in vivo deposition and hypoglycaemic activity after delivery to rat lungs. J Control Release 127(3):257–266

    Article  CAS  Google Scholar 

  140. Obata H et al (2008) Single injection of a sustained-release prostacyclin analog improves pulmonary hypertension in rats. Am J Respir Crit Care Med 177(2):195–201

    Article  PubMed  CAS  Google Scholar 

  141. Bakker-Woudenberg IA et al (2001) Improved efficacy of ciprofloxacin administered in polyethylene glycol-coated liposomes for treatment of Klebsiella pneumoniae pneumonia in rats. Antimicrob Agents Chemother 45(5):1487–1492

    Article  PubMed  CAS  Google Scholar 

  142. Farkas L et al (2009) VEGF ameliorates pulmonary hypertension through inhibition of endothelial apoptosis in experimental lung fibrosis in rats. J Clin Invest 119(5):1298–1311

    Article  PubMed  CAS  Google Scholar 

  143. Keenan RJ et al (1992) Improved immunosuppression with aerosolized cyclosporine in experimental pulmonary transplantation. Transplantation 53(1):20–25

    Article  PubMed  CAS  Google Scholar 

  144. Hitzman CJ, Wattenberg LW, Wiedmann TS (2006) Pharmacokinetics of 5-fluorouracil in the hamster following inhalation delivery of lipid-coated nanoparticles. J Pharm Sci 95(6):1196–1211

    Article  PubMed  CAS  Google Scholar 

  145. Sandrasagra A et al (2001) RASONs: a novel antisense oligonucleotide therapeutic approach for asthma. Expert Opin Biol Ther 1(6):979–983

    Article  PubMed  CAS  Google Scholar 

  146. Miller TL et al (2005) Recombinant human Clara cell secretory protein in acute lung injury of the rabbit: effect of route of administration. Pediatr Crit Care Med 6(6):698–706

    Article  PubMed  Google Scholar 

  147. Casarosa P et al (2009) Preclinical evaluation of long-acting muscarinic antagonists: comparison of tiotropium and investigational drugs. J Pharmacol Exp Ther 330(2):660–668

    Article  PubMed  CAS  Google Scholar 

  148. Rodriguez CO et al (2009) Aerosol gemcitabine: preclinical safety and in vivo antitumor activity in osteosarcoma-bearing dogs. J Aerosol Med Pulm Drug Deliv 22(4):1–10

    Google Scholar 

  149. Selting K et al (2008) Feasibility and safety of targeted cisplatin delivery to a select lung lobe in dogs via the AeroProbe intracorporeal nebulization catheter. J Aerosol Med Pulm Drug Deliv 21(3):255–268

    Article  PubMed  CAS  Google Scholar 

  150. Sanjar S, Matthews J (2001) Treating systemic diseases via the lung. J Aerosol Med 14(Suppl 1):S51–S58

    Article  PubMed  CAS  Google Scholar 

  151. Jansen M et al (2004) Pulmonary delivery of TH9507, a growth hormone releasing factor analogue, in the dog. Int J Pharm 276(1–2):75–81

    Article  PubMed  CAS  Google Scholar 

  152. Bennett DB et al (1994) Pulmonary delivery of detirelix by intratracheal instillation and aerosol inhalation in the briefly anesthetized dog. Pharm Res 11(7):1048–1055

    Article  PubMed  CAS  Google Scholar 

  153. Sood BG et al (2008) Aerosol delivery in ventilated newborn pigs: an MRI evaluation. Pediatr Res 64(2):159–164

    Article  PubMed  Google Scholar 

  154. Morita N et al (2006) Aerosolized alpha-tocopherol ameliorates acute lung injury following combined burn and smoke inhalation injury in sheep. Shock 25(3):277–282

    Article  PubMed  CAS  Google Scholar 

  155. Cox CA et al (2001) Intratracheal administration of perfluorochemical-gentamicin suspension: a comparison to intravenous administration in normal and injured lungs. Pediatr Pulmonol 32(2):142–151

    Article  PubMed  CAS  Google Scholar 

  156. Desigaux L et al (2005) Nonionic amphiphilic block copolymers promote gene transfer to the lung. Hum Gene Ther 16:821–829

    Article  PubMed  CAS  Google Scholar 

  157. Lechner AJ, Banchero N (1982) Advanced pulmonary development in newborn guinea pigs (Cavia porcellus). Am J Anat 163:235–246

    Article  PubMed  CAS  Google Scholar 

  158. Wagner JE, Manning PJ (1976) The biology of the guinea pig. Academic, New York

    Google Scholar 

  159. McMurray DN (1994) Guinea pig model of tuberculosis. In: Bloom B (ed) Tuberculosis: pathogenesis, protection, and control. ASM Press, Washington, pp 135–148

    Google Scholar 

  160. Spond J et al (2003) Inhibition of experimental acute pulmonary inflammation by pirfenidone. Pulm Pharmacol Ther 16:207–214

    Article  PubMed  CAS  Google Scholar 

  161. Surendrakumar K et al (2003) Sustained release of insulin from sodium hyaluronate based dry powder formulations after pulmonary delivery to beagle dogs. J Control Release 91:385–394

    Article  PubMed  CAS  Google Scholar 

  162. Murakami K et al (2002) A novel animal model of sepsis after acute lung injury in sheep. Crit Care Med 30(9):2083–2090

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pharmaceutical Sciences, College of Pharmacy, The University of Oklahoma Health Sciences Center, 1110 N. Stonewall Avenue, Oklahoma City, OK, 73126, USA

    Lucila Garcia-Contreras

Authors
  1. Lucila Garcia-Contreras
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Lucila Garcia-Contreras .

Editor information

Editors and Affiliations

  1. , Pharmaceutics Division - PHR 4.214, University of Texas, University Station 1, Austin, 78712, USA

    Hugh D.C. Smyth

  2. Eshelman School of Pharmacy, Division of Molecular Pharmaceutics, University of North Carolina, Chapel Hill, 27599, North Carolina, USA

    Anthony J. Hickey

Rights and permissions

Reprints and permissions

Copyright information

© 2011 Controlled Release Society

About this chapter

Cite this chapter

Garcia-Contreras, L. (2011). In Vivo Animal Models for Controlled-Release Pulmonary Drug Delivery. In: Smyth, H., Hickey, A. (eds) Controlled Pulmonary Drug Delivery. Advances in Delivery Science and Technology. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-9745-6_19

Download citation

Publish with us

Policies and ethics

Societies and partnerships

Search

Navigation