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Controlled Transport for Pulmonary Drug Delivery

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Controlled Pulmonary Drug Delivery

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

Abstract

Interactions between inhaled particles and the respiratory tract fluids are important for inhaled drug delivery systems. In particular, controlling the transport of aerosol particles after deposition in the respiratory tract may improve drug retention time in the lungs, allow targeting, and facilitate optimal transport through innate defense mechanisms of the lung. In this chapter the mechanisms by which particles can transport in the lungs and the aerosol design criteria for improving particle residence times or promoting uniform distribution across or within the lung space are discussed.

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References

  1. Ganguly S, Moolchandani V, Roche JA, Shapiro PS, Somaraju S, Eddington ND et al (2008) Phospholipid-induced in-vivo particle migration to enhance pulmonary deposition. J Aerosol Med Pulm Drug Deliv 4:343–350

    Article  Google Scholar 

  2. Haitsma JJ, Lachmann U, Lachmann B (2001) Exogenous surfactant as a drug delivery agent. Adv Drug Deliv Rev 47(2–3):197–207

    Article  PubMed  CAS  Google Scholar 

  3. Marcinkowski AL, Garoff S, Tilton RD, Pilewski JM, Corcoran TE (2008) Postdeposition dispersion of aerosol medications using surfactant carriers. J Aerosol Med Pulm Drug Deliv 4:361–369

    Article  Google Scholar 

  4. Im Hof V, Gehr P, Gerber V, Lee MM, Schürch S (1997) In vivo determination of surface tension in the horse trachea and in vitro model studies. Respir Physiol 109(1):81–93

    Article  PubMed  CAS  Google Scholar 

  5. Schürch S, Gehr P, Im Hof V, Geiser M, Green F (1990) Surfactant displaces particles toward the epithelium in airways and alveoli. Respir Physiol 80(1):17–32

    Article  PubMed  Google Scholar 

  6. Rubin BK (2009) Mucus, phlegm, and sputum in cystic fibrosis. Respir Care 54(6):726–732

    Article  PubMed  Google Scholar 

  7. King M, Rubin BK (1999) Mucus-controlling agents: past and present. Respir Care Clin N Am 5(4):575–594

    PubMed  CAS  Google Scholar 

  8. Hohlfeld JM (2002) The role of surfactant in asthma. Respir Res 3:4

    Article  PubMed  Google Scholar 

  9. Banerjee R, Puniyani RR (2000) Exogenous surfactant therapy and mucus rheology in chronic obstructive airway diseases. J Biomater Appl 14(3):243–272

    Article  PubMed  CAS  Google Scholar 

  10. Widdicombe JG (1997) Airway liquid: a barrier to drug diffusion? Eur Respir J 10(10):2194–2197

    Article  PubMed  CAS  Google Scholar 

  11. Widdicombe JH, Bastacky SJ, Wu DX, Lee CY (1997) Regulation of depth and composition of airway surface liquid. Eur Respir J 10(12):2892–2897

    Article  PubMed  CAS  Google Scholar 

  12. Morgenroth K (1985) Morphology of the bronchial lining layer and its alteration in IRDS, ARDS and COLD. J Respir Dis Suppl 142:7–18

    CAS  Google Scholar 

  13. Kharasch VS, Sweeney TD, Fredberg J, Lehr J, Damokosh AI, Avery ME et al (1991) Pulmonary surfactant as a vehicle for intratracheal delivery of technetium sulfur colloid and pentamidine in hamster lungs. Am Rev Respir Dis 144(4):909–913

    PubMed  CAS  Google Scholar 

  14. van’t Veen A, Mouton JW, Gommers D, Lachmann B (1996) Pulmonary surfactant as vehicle for intratracheally instilled tobramycin in mice infected with Klebsiella pneumoniae. Br J Pharmacol 119(6):1145–1148

    PubMed  Google Scholar 

  15. Grotberg JB, Halpern J, Jensen OE (1995) Interaction of exogenous and endogenous surfactant: spreading-rate effects. J Appl Physiol 78(2):750–756

    PubMed  CAS  Google Scholar 

  16. Gommers D, Haitsma JJ, Lachmann B (2006) Surfactant as a carrier: influence of immunosuppressive agents on surfactant activity. Clin Physiol Funct Imaging 26(6):357–361

    Article  PubMed  CAS  Google Scholar 

  17. Chimote G, Banerjee R (2009) Evaluation of antitubercular drug-loaded surfactants as inhalable drug-delivery systems for pulmonary tuberculosis. J Biomed Mater Res A 89(2):281–292

    PubMed  CAS  Google Scholar 

  18. Zhang YL, Matar OK, Craster RV (2003) A theoretical study of chemical delivery within the lung using exogenous surfactant. Med Eng Phys 25:115–132

    Article  PubMed  Google Scholar 

  19. Geiser M, Leupin N, Maye I (2000) Im Hof V, Gehr P. Interaction of fungal spores with the lungs: distribution and retention of inhaled puffball (calvatia excipuliformis) spores. J Allergy Clin Immunol 106:92–100

    Article  PubMed  CAS  Google Scholar 

  20. Gehr P, Schürch S, Berthiaume Y, Im Hof V, Geiser M (1990) Particle retention in airways by surfactant. J Aerosol Med 3:27–43

    Article  Google Scholar 

  21. Geiser M, Cruz-Orive LM, Im Hof V, Gehr P (1990) Assessment of particle retention and clearance in the intrapulmonary conducting airways of hamster lungs with the fractionator. J Microsc 160:75–88

    PubMed  CAS  Google Scholar 

  22. Geiser M, Cruz-Orive LM, Waber U, Im Hof V, Gehr P (1995) Particle retention in airways estimated by unbiased stereology and photometry. J Aerosol Med 8:149–165

    Article  Google Scholar 

  23. Geiser M, Gerber P, Maye I, Im Hof V, Gehr P (2000) Retention of teflon particles in hamster lungs: a stereological study. J Aerosol Med 13:43–55

    Article  PubMed  CAS  Google Scholar 

  24. Schürch S, Geiser M, Lee MM, Gehr P (1999) Particles at the airway interfaces of the lung. Colloids Surf B Biointerfaces 15(3–4):339–353

    Article  Google Scholar 

  25. Gerber P, Lehmann C, Gehr P, Schürch S (2006) Wetting and spreading of a surfactant film on solid particles: influence of sharp edges and surface irregularities. Langmuir 22(12):5273–5281

    Article  PubMed  CAS  Google Scholar 

  26. Wine JJ (1999) The genesis of cystic fibrosis lung disease. J Clin Invest 103:309–312

    Article  PubMed  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  28. Song Y, Namkung W, Nielson DW, Lee J, Finkbeiner WE, Verkman AS (2009) Surface liquid depth measured in ex vivo fragments of pig and human trachea: dependence on Na+ and Cl− channel function. Am J Physiol Lung Cell Mol Physiol 297:L1131–L1140

    Article  PubMed  CAS  Google Scholar 

  29. Jayaraman S, Song Y, Vetrivel L, Shankar L, Verkman AS (2001) Noninvasive in vivo fluorescence measurement of airway-surface liquid depth, salt concentration, and pH. J Clin Invest 107:317–324

    Article  PubMed  CAS  Google Scholar 

  30. Sanders N, Rudolph C, Braeckmans K, De Smedt SC, Demeester J (2009) Extracellular barriers in respiratory gene therapy. Adv Drug Deliv Rev 61:115–127

    Article  PubMed  CAS  Google Scholar 

  31. Fiegel J, Jin F, Hanes J, Stebe K (2005) Wetting of a particle in a thin film. J Coll Int Sci 291:507–514

    Article  CAS  Google Scholar 

  32. Geiser M, Schurch S, Gehr P (2003) Influence of surface chemistry and topography of particles on their immersion into the lung’s surface-lining layer. J Appl Physiol 94:1793–1801

    PubMed  Google Scholar 

  33. Lansley AB, Sanderson MJ, Dirksen ER (1992) Control of the beat cycle of respiratory tract cilia by Ca2+ and cAMP. Am J Physiol Lung Cell Mol Physiol 263(2):L323–L324

    Google Scholar 

  34. Tarran R, Trout L, Donaldson SH, Boucher RC (2006) Soluble mediators, not cilia, determine airway surface liquid volume in normal and cystic fibrosis superficial airway epithelia. J Gen Physiol 127(5):591–604

    Article  PubMed  CAS  Google Scholar 

  35. Cone RA (2009) Barrier properties of mucus. Adv Drug Del Rev 61:75–85

    Article  CAS  Google Scholar 

  36. King M, Rubin BK (2002) Pharmacological approaches to discovery and development of new mucolytic agents. Adv Drug Del Rev 54:1475–1490

    Article  CAS  Google Scholar 

  37. Wolff RK (1986) Effects of airborne pollutants on mucociliary clearance. Environ Health Perspect 66:223–237

    Article  PubMed  CAS  Google Scholar 

  38. Hermens WAJJ, Merkus FWHM (1987) The influence of drugs on nasal ciliary movement. Pharm Res 4(6):445–449

    Article  PubMed  CAS  Google Scholar 

  39. Matsui H, Grubb BR, Tarran R, Randell SH, Gatzy JT, Davis CW et al (1998) Evidence for periciliary liquid layer depletion, not abnormal ion composition, in the pathogenesis of cystic fibrosis airways disease. Cell 95:1005–1015

    Article  PubMed  CAS  Google Scholar 

  40. Kuperman DA, Huang X, Koth LL, Chang GH, Doganov GM, Zhu Z et al (2002) Direct effects of interleukin-13 on epithelial cells cause airway hyperreactivity and mucus overproduction in asthma. Nat Med 8:885–889

    PubMed  CAS  Google Scholar 

  41. Vestbo J, Prescott E, Lange P (1996) Association of chronic mucus hypersecretion with FEV1 decline and chronic obstructive pulmonary disease morbidity. copenhagen city heart study group. Am J Respir Crit Care Med 153(5):1530–1535

    PubMed  CAS  Google Scholar 

  42. Aikawa T, Shimura S, Sasaki H, Ebina M, Takishima T (1992) Marked goblet cell hyperplasia with mucus accumulation in the airways of patients who died of severe acute asthma attack. Chest 101(4):916–921

    Article  PubMed  CAS  Google Scholar 

  43. Robinson M, Eberl S, Tomlinson C, Daviskas E, Regnis JA, Bailey DL et al (2000) Regional mucociliary clearance in patients with cystic fibrosis. J Aerosol Med 13(2):73–86

    Article  PubMed  CAS  Google Scholar 

  44. Yu CP, Hu JP, Yen BM, Spektor DM, Lippmann M (1986) Models for mucociliary particle clearance in lung airways. In: Lee SD, Schneider T, Grant LD, Verkerk PJ (eds) Aerosols. Lewis Publishers, Michigan

    Google Scholar 

  45. Lippmann M (1986) Respiratory tract deposition and clearance of aerosols. In: Lee SD, Schneider T, Grant LD, Verkerk PJ (eds) Aerosols. Lewis Publishers, Michigan

    Google Scholar 

  46. Donaldson SH, Bennett WD, Zeman KL, Knowles MR, Tarran R, Boucher RC (2006) Mucus clearance and lung function in cystic fibrosis with hypertonic saline. N Engl J Med 354(3):241–250

    Article  PubMed  CAS  Google Scholar 

  47. Rubin BK (2007) Mucolytics, expectorants, and mucokinetic medications. Respir Care 52(7):859–865

    PubMed  Google Scholar 

  48. Houtmeyers E, Gosselink R, Gayan-Ramirez G, Decramer M (1999) Effects of drugs on mucus clearance. Eur Respir J 14:452–467

    Article  PubMed  CAS  Google Scholar 

  49. Lai SK, Wang Y, Wirtz D, Hanes J (2009) Micro- and macrorheology of mucus. Am J Respir Cell Mol Biol 61:86–100

    CAS  Google Scholar 

  50. Foster WM, Bergofsky EH, Bohning DE, Lippmann M, Albert RE (1976) Effect of adrenergic agents and their mode of action on mucociliary clearance in man. J Appl Physiol 41(2):146–152

    PubMed  CAS  Google Scholar 

  51. Foster WM, Langenback E, Bergofsky EH (1980) Measurement of tracheal and bronchial mucus velocities in man: relation to lung clearance. J Appl Physiol 48(6):965–971

    PubMed  CAS  Google Scholar 

  52. Lafortuna CL, Fazio F (1984) Acute effect of inhaled salbutamol on mucociliary clearance in health and chronic bronchitis. Respiration 45:111–123

    Article  PubMed  CAS  Google Scholar 

  53. Mortensen J, Lange P, Nyboe J, Groth S (1994) Lung mucociliary clearance. Eur J Nucl Med 21(9):953–961

    Article  PubMed  CAS  Google Scholar 

  54. Groth S, Mortensen J, Lange P, Munch EP, Sorensen PG, Rossing N (1988) Imaging of the airways by bronchoscintigraphy for the study of mucociliary clearance. Thorax 43(5):360–365

    Article  PubMed  CAS  Google Scholar 

  55. Yeates DB, Aspin N, Levison H, Jones MT, Bryan AC (1975) Mucociliary tracheal transport rates in man. J Appl Physiol 39(3):487–495

    PubMed  CAS  Google Scholar 

  56. Knowles MR, Clarke LL, Boucher RC (1991) Activation by extracellular nucleotides of chloride secretion in the airway epithelia of patients with cystic fibrosis. N Engl J Med 325(8):533–538

    Article  PubMed  CAS  Google Scholar 

  57. Benali R, Pierrot D, Zahm JM, de Bentzmann S, Puchelle E (1994) Effects of extracellular ATP and UTP on fluid transport by human nasal epithelial cells in culture. Am J Respir Cell Mol Biol 10:363–368

    PubMed  CAS  Google Scholar 

  58. Merten MD, Breittmayer JP, Figarella C, Frelin C (1993) ATP and UTP increase secretion of bronchial inhibitor by human tracheal gland cells in culture. Am J Physiol Lung Cell Mol Physiol 265(5):L479–L484

    CAS  Google Scholar 

  59. Olivier KN, Bennett WD, Hohneker KW, Boucher RC, Knowles MR (1996) Acute safety and effects on mucociliary clearance of aerosolized uridine 5′-triphosphateamiloride in normal human adults. Am J Respir Crit Care Med 154:217–223

    PubMed  CAS  Google Scholar 

  60. Cammer P, Strandberg K, Philipson K (1974) Increased mucociliary transport by cholinergic stimulation. Arch Environ Health 29:220–224

    PubMed  CAS  Google Scholar 

  61. Wilson R (1988) Secondary ciliary dysfunction. Clin Sci 75:113–120

    PubMed  CAS  Google Scholar 

  62. Wilson R, Pitt T, Taylor G, Watson D, MacDermot J, Sykes D et al (1987) Pyocyanin and 1-hydroxyphenazine produced by pseudomonas aeruginosa inhibit the beating of human respiratory cilia in vitro. J Clin Invest 79(1):221–229

    Article  PubMed  CAS  Google Scholar 

  63. Read RC, Roberts P, Munro N, Rutman A, Hastie A, Shryock T et al (1992) Effect of pseudomonas aeruginosa rhamnolipids on mucociliary transport and ciliary beating. J Appl Physiol 72(6):2271–2277

    PubMed  CAS  Google Scholar 

  64. Wilson R, Moxon BR (1988) Molecular basis of Haemophilus influenzae pathogenicity in the respiratory tract. In: Griffiths E, Donachie W, Stephen J (eds) Bacterial infections of respiratory and gastrointestinal mucosae. IRL Press, Oxford, pp 29–40

    Google Scholar 

  65. Steinfort C, Wilson R, Mitchell T, Feldman C, Rutman A, Todd H et al (1989) Effect of Streptococcus pneumoniae on human respiratory epithelium in vitro. Infect Immun 57(7):2006–2013

    PubMed  CAS  Google Scholar 

  66. Moller W, Haussinger K, Winkler-Heil R, Stahlhofen W, Meyer T, Hofmann W et al (2004) Mucociliary and long-term particle clearance in the airways of healthy nonsmoker subjects. J Appl Physiol 97(6):2200–2206

    Article  PubMed  Google Scholar 

  67. Stahlhofen W, Koebrich R, Rudolf G, Scheuch G (1990) Short-term and long-term clearance of particles from the upper human respiratory tract as function of particle size. J Aerosol Sci 21(Suppl 1):S407–S410

    Article  Google Scholar 

  68. Huang Y, Leobandung W, Foss A, Peppas NA (2000) Molecular aspects of muco- and bioadhesion: tethered structures and site-specific surfaces. J Control Release 65(1–2):63–71

    Article  PubMed  CAS  Google Scholar 

  69. De Ascentiis A, deGrazia JL, Bowman CN, Colombo P, Peppas NA (1995) Mucoadhesion of poly(2-hydroxyethyl methacrylate) is improved when linear poly(ethylene oxide) chains are added to the polymer network. J Control Release 33(1):197–201

    Article  Google Scholar 

  70. Sakagami M, Kinoshita W, Sakon K, Sato J, Makino Y (2002) Mucoadhesive beclomethasone microspheres for powder inhalation: their pharmacokinetics and pharmacodynamics evaluation. J Control Release 80(1–3):207–218

    Article  PubMed  CAS  Google Scholar 

  71. Surendrakumar K, Martyn GP, Hodgers ECM, Jansen M, Blair JA (2003) Sustained release of insulin from sodium hyaluronate based dry powder formulations after pulmonary delivery to beagle dogs. J Control Release 91(3):385–394

    Article  PubMed  CAS  Google Scholar 

  72. Hwang SM, Kim DD, Chung SJ, Shim CK (2008) Delivery of ofloxacin to the lung and alveolar macrophages via hyaluronan microspheres for the treatment of tuberculosis. J Control Release 129(2):100–106

    Article  PubMed  CAS  Google Scholar 

  73. Boat TF, Cheng PW (1980) Biochemistry of airway mucus secretions. Fed Proc 39(13):3067–3074

    PubMed  CAS  Google Scholar 

  74. Thornton DJ, Sheehan JK (2004) From mucins to mucus: toward a more coherent understanding of this essential barrier. Proc Am Thorac Soc 1(1):54–61

    Article  PubMed  CAS  Google Scholar 

  75. Zayas G, Dimitry J, Zayas A, O’Brien D, King M (2005) A new paradigm in respiratory hygiene: Increasing the cohesivity of airway secretions to improve cough interaction and reduce aerosol dispersion. BMC Pulm Med 5:11

    Article  PubMed  Google Scholar 

  76. Radomsky ML, Whaley KJ, Cone RA, Saltzman WM (1990) Macromolecules released from polymers: diffusion into unstirred fluids. Biomaterials 11:619–624

    Article  PubMed  CAS  Google Scholar 

  77. Henry BT, Hibberd AS, Cheema MS, Davis SS, Rogers TG (1992) Epi-fluorescence microscopy and image analysis used to measure diffusion coefficients in gel systems. J Pharm Pharmacol 44:543–549

    Article  PubMed  CAS  Google Scholar 

  78. Saltzman WM, Radomsky ML, Whaley KJ, Cone RA (1994) Antibody diffusion in human cervical mucus. Biophys J 66(2, Part 1):508–815

    Google Scholar 

  79. Olmsted SS, Padgett JL, Yudin AI, Whaley KJ, Moench TR, Cone RA (2001) Diffusion of macromolecules and virus-like particles in human cervical mucus. Biophys J 81(4):1930–1937

    Article  PubMed  CAS  Google Scholar 

  80. Broughton-Head VJ, Smith JR, Shur J, Shute JK (2007) Actin limits enhancement of nanoparticle diffusion through cystic fibrosis sputum by mucolytics. Pulm Pharmacol Ther 20(6):708–717

    Article  PubMed  CAS  Google Scholar 

  81. Sanders NN, DeSmedt SC, Van Rompaev E, Simoens P, De Baets F, Demeester J (2000) Cystic fibrosis sputum – a barrier to the transport of nanospheres. Am J Respir Crit Care Med 162:1905–1911

    PubMed  CAS  Google Scholar 

  82. Voynow JA, Rubin BK (2009) Mucins, mucus, and sputum. Chest 135(2):505–512

    Article  PubMed  CAS  Google Scholar 

  83. Bolister N, Basker M, Hodges NA, Marriott C (1991) The diffusion of B-lactam antibiotics through mixed gels of cystic fibrosis-derived mucin and pseudomonas aeruginosa alginate. J Antimicrob Chemother 27:285–293

    Article  PubMed  CAS  Google Scholar 

  84. Sanders NN, Van Rompaev E, DeSmedt SC, Demeester J (2002) On the transport of lipoplexes through cystic fibrosis sputum. Pharm Res 19(4):451–456

    Article  PubMed  CAS  Google Scholar 

  85. Sanders NN, DeSmedt SC, Demeester J (2003) Mobility and stability of gene complexes in biogels. J Control Release 87:117–129

    Article  PubMed  CAS  Google Scholar 

  86. Broughton-Head VJ, Shur J, Carroll MP, Smith JR, Shute JK (2007) Unfractionated heparin reduces the elasticity of sputum from patients with cystic fibrosis. Am J Physiol Lung Cell Mol Physiol 293:L1240–L1249

    Article  PubMed  CAS  Google Scholar 

  87. Kas HS (1997) Chitosan: properties, preparations and application to microparticulate systems. J Microencapsul 14(6):689–711

    Article  PubMed  CAS  Google Scholar 

  88. Sanders NN, Van Rompaev E, DeSmedt SC, Demeester J (2001) Structural alterations of gene complexes by cystic fibrosis sputum. Am J Respir Crit Care Med 164:486–493

    PubMed  CAS  Google Scholar 

  89. Dawson M, Wirtz D, Hanes J (2003) Enhanced viscoelasticity of human cystic fibrotic sputum correlates with increasing microheterogeneity in particle transport. J Biol Chem 278:50393–50401

    Article  PubMed  CAS  Google Scholar 

  90. Wada A, Nakamura H (1981) Nature of the charge distribution in proteins. Nature 5835:757–758

    Article  Google Scholar 

  91. Suk JS, Lai SK, Wang Y, Ensign LM, Zeitlin PL, Boyle MP et al (2009) The penetration of fresh undiluted sputum expectorated by cystic fibrosis patients by non-adhesive polymer nanoparticles. Biomaterials 30(13):2591–2597

    Article  PubMed  CAS  Google Scholar 

  92. Wang Y, Lai SK, Suk JS, Pace A, Cone R, Hanes J (2008) Addressing the PEG mucoadhesivity paradox to engineer nanoparticles that “slip” through the human mucus barrier. Angew Chem Int Ed 47:9726–9729

    Article  CAS  Google Scholar 

  93. Carrabino S, Di Gioia S, Copreni E, Conese M (2005) Serum albumin enhanced polyethyleneimine-mediated gene delivery to human respiratory epithelial cells. J Gene Med 7:1555–1564

    Article  PubMed  CAS  Google Scholar 

  94. Stern M, Caplen NJ, Browning JE, Griesenbach U, Sorgi F, Huang L et al (1998) The effect of mucolytic agents on gene transfer across a CF sputum barrier in vitro. Gene Therapy 5:91–98

    Article  PubMed  CAS  Google Scholar 

  95. Scherer F, Anton M, Schillinger U, Henke J, Kruger A, Gansbacher B (2002) Magnetofection: enhancing and targeting gene delivery by magnetic force in vitro and in vivo. Gene Therapy 9:102–109

    Article  PubMed  CAS  Google Scholar 

  96. Xenariou S, Griesenbach U, Liang H, Zhu J, Farley R, Somerton L et al (2007) Use of ultrasound to enhance nonviral lung gene transfer in vivo. Gene Therapy 14:768–774

    Article  PubMed  CAS  Google Scholar 

  97. James AC (1988) Lung dosimetry. In: Nazaroff WW, Nero AV Jr (eds) Radon and its decay products in indoor air. Wiley, New York

    Google Scholar 

  98. Gehr P (1994) Anatomy and morphology of the respiratory tract. In: ICRP (eds) Human respiratory tract model for radiological protection. ICRP publication 66. Ann ICRP 24(1–3):121–166

    Google Scholar 

  99. ICRP (1999) Human respiratory tract model for radiological protection. ICRPpublication 66. Ann ICRP 24(1–3):1–482

    Google Scholar 

  100. Lai SK, O’Hanlon DE, Harrold S, Man ST, Wang Y, Cone R et al (2007) Rapid transport of large polymeric nanoparticles in fresh undiluted human mucus. Proc Natl Acad Sci 104(5):1482–1487

    Article  PubMed  CAS  Google Scholar 

  101. Lessard GA, Goodwin PM, Werner JH (2007) Three-dimensional tracking of individual quantum dots. Appl Phys Lett 91(22):224106

    Article  Google Scholar 

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Authors and Affiliations

  1. Department of Pharmaceutical Sciences and Experimental Therapeutics and Department of Chemical and Biochemical Engineering, The University of Iowa, 115 S. Grand Avenue, S215 PHAR, Iowa City, IA, 52242, USA

    Jennifer Fiegel

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  1. Jennifer Fiegel
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  2. Timothy Brenza
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  3. Rania Hamed
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Correspondence to Jennifer Fiegel .

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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

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© 2011 Controlled Release Society

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Fiegel, J., Brenza, T., Hamed, R. (2011). Controlled Transport for 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_7

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