Challenges and advances in the development of inhalable drug formulations for cystic fibrosis lung disease

Expert Opinion on Drug Delivery

Volumn 8, Issue 4, 2011, Pages 451-466

  Ibrahim, Basma M ^a   Tsifansky, Michael D ^b   Yang, Yan ^c   Yeo, Yoon ^a,d  

^a PURDUE UNIVERSITY   (United States)

^b Advocate Lutheran General Children's Hospital   (United States)

^c JILIN UNIVERSITY   (China)

^d PURDUE UNIVERSITY   (United States)

Author keywords

Cystic fibrosis; drug delivery system; inhalation; lung disease; sputum

Indexed keywords

ACETYLCYSTEINE; ADENOVIRUS VECTOR; AGENTS AFFECTING PROTEIN METABOLISM; AMINOGLYCOSIDE; AMOXICILLIN PLUS CLAVULANIC ACID; AMPHOTERICIN B; ANTIBIOTIC AGENT; ANTIINFLAMMATORY AGENT; ATALUREN; AZITHROMYCIN; BETA LACTAM ANTIBIOTIC; BRONCHODILATING AGENT; CHOLINERGIC RECEPTOR BLOCKING AGENT; CIPROFLOXACIN; CLINDAMYCIN; COLISTIN; CORTICOSTEROID; COTRIMOXAZOLE; DORNASE ALFA; GENTAMICIN; IBUPROFEN; LINEZOLID; MACROLIDE; MANNITOL; QUINOLINE DERIVED ANTIINFECTIVE AGENT; SMALL INTERFERING RNA; TOBRAMYCIN; TRANSMEMBRANE CONDUCTANCE REGULATOR; UNCLASSIFIED DRUG; UNINDEXED DRUG; VX 770;

ANTIBIOTIC RESISTANCE; ANTICHOLINERGIC EFFECT; ANTIINFLAMMATORY ACTIVITY; ASPERGILLUS FUMIGATUS; ATYPICAL MYCOBACTERIOSIS; BIOFILM; BREATHING EXERCISE; BRONCHIECTASIS; BURKHOLDERIA CEPACIA COMPLEX; BURKHOLDERIA INFECTION; CYSTIC FIBROSIS; DRUG FORMULATION; DRUG TRANSPORT; DRY POWDER; GENE MUTATION; GENE SILENCING; GENE TARGETING; GENETIC TRANSFECTION; GLYCOCALYX; HAEMOPHILUS INFLUENZAE; HUMAN; INHALATIONAL DRUG ADMINISTRATION; INHALER; LIPOSOMAL DELIVERY; LIPOSOMAL GENE DELIVERY SYSTEM; MAGNETISM; MUCOCILIARY CLEARANCE; MUCOLYSIS; NONVIRAL GENE DELIVERY SYSTEM; PARTICLE SIZE; PSEUDOMONAS AERUGINOSA; PSEUDOMONAS INFECTION; RESPIRATORY TRACT INFECTION; RESPIRATORY TRACT INFLAMMATION; REVIEW; RNA INTERFERENCE; SCANNING ELECTRON MICROSCOPY; SPUTUM; SPUTUM VISCOSITY; STAPHYLOCOCCUS AUREUS; STAPHYLOCOCCUS INFECTION; STENOTROPHOMONAS MALTOPHILIA; SYSTEMIC INFLAMMATORY RESPONSE SYNDROME; TRANSMISSION ELECTRON MICROSCOPY; VIRAL GENE DELIVERY SYSTEM; VIRUS LIKE AGENT; VISCOELASTICITY;

ADMINISTRATION, INHALATION; ANIMALS; CHEMISTRY, PHARMACEUTICAL; CYSTIC FIBROSIS; DRUG DELIVERY SYSTEMS; GENE TRANSFER TECHNIQUES; HUMANS; LUNG; PHARMACEUTICAL PREPARATIONS; SPUTUM;

EID: 79952912550     PISSN: 17425247     EISSN: None     Source Type: Journal    
DOI: 10.1517/17425247.2011.561310     Document Type: Review

References (214)

1. Cystic Fibrosis Foundation. Available from: Http://www.cff.org [Last accessed 19 October 2010]
2. Farrell PM, Rosenstein BJ, White TB, et al. Guidelines for diagnosis of cystic fibrosis in newborns through older adults: Cystic fibrosis foundation consensus report. The J Pediatrics 2008;153(2):S4-14 (Pubitemid 351970581)
3. Cystic Fibrosis Mutation Database. Available from: Http://www.genet. sickkids.on.ca/cftr [Last accessed 19 October 2010]
4. Wilschanski M, Durie PR. Patterns of GI disease in adulthood associated with mutations in the CFTR gene. Gut 2007;56(8):1153-63 (Pubitemid 47123248)
5. Watson MS, Cutting GR, Desnick RJ, et al. Cystic fibrosis population carrier screening: 2004 revision of American College of Medical Genetics mutation panel. Genet Med 2004;6(5):387-91 (Pubitemid 39310514)
6. Cotran RS, Kumar V, Collins T, et al. Robbins pathologic basis of disease. Saunders, Philadelphia; 1999
7. Ramsey BW. Management of pulmonary disease in patients with cystic fibrosis. N Engl J Med 1996;335:179-88 (Pubitemid 26249456)
8. Clunes MT, Boucher RC. Cystic fibrosis: The mechanisms of pathogenesis of an inherited lung disorder. Drug Discov Today Dis Mech 2007;4(2):63-72 (Pubitemid 351966331)
9. Clunes MT, Boucher RC. Front-runners for pharmacotherapeutic correction of the airway ion transport defect in cystic fibrosis. Curr Opin Pharmacol 2008;8(3):292-9
10. Rubin BK. Mucus, phlegm, and sputum in cystic fibrosis. Respir Care 2009;54(6):726-32. Definition of mucus, phlegm and sputum.
11. Rubin BK. Mucus and mucins. Otolaryngol Clin North Am 2010;43(1):27-34
12. Murphy TM, Rosenstein BJ. Advances in the science and treatment of cystic fibrosis lung diseases: A continuing medical education resource. Duke University Medical Center & Health System; Durham, North Carolina 1998. A comprehensive overview of CF disease and therapy.
13. Sanders NN, De Smedt SC, Van Rompaey E, et al. Cystic fibrosis sputum: A barrier to the transport of nanospheres. Am J Respir Crit Care Med 2000;162(5):1905-11. Early study on hindrance of nanoparticle transport in CF mucus.
14. Cohn JA, Neoptolemos JP, Feng J, et al. Increased risk of idiopathic chronic pancreatitis in cystic fibrosis carriers. Hum Mutat 2005;26(4):303-7 (Pubitemid 41361797)
15. Shahram B, Anders E, Johan A, et al. Cystic fibrosis gene mutations and gastrointestinal diseases. J Cyst Fibros 2010;9(4):288-91
16. Wang X, Kim J, McWilliams R, et al. Increased prevalence of chronic rhinosinusitis in carriers of a cystic fibrosis mutation. Arch Otolaryngol Head Neck Surg 2005;131(3):237-40 (Pubitemid 40349923)
17. Ziedalski TM, Kao PN, Henig NR, et al. Prospective analysis of cystic fibrosis transmembrane regulator mutations in adults with bronchiectasis or pulmonary nontuberculous mycobacterial infection. Chest 2006;130(4):995-1002 (Pubitemid 44583727)
18. Wang X, Moylan B, Leopold DA, et al. Mutation in the gene responsible for cystic fibrosis and predisposition to chronic rhinosinusitis in the general population. JAMA 2000;284(14):1814-19
19. Girodon E, Cazeneuve C, Lebargy F, et al. CFTR gene mutations in adults with disseminated bronchiectasis. Eur J Hum Genet 1997;5(3):149-55 (Pubitemid 27356702)
20. Kunzelmann K, Mall M. Pharmacotherapy of the ion transport defect in cystic fibrosis. Clin Exp Pharmacol Physiol 2001;28(11):857-67 (Pubitemid 33071055)
21. Rubin BK. Emeging therapies for cystic fibrosis lung disease. Chest 1999;115:1120-6 (Pubitemid 29193687)
22. Grasemann H, Ratjen F. Emerging therapies for cystic fibrosis lung disease. Expert Opin Emerg Drugs 2010;15(4):653-9
23. Anderson P. Emerging therapies in cystic fibrosis. Ther Adv Respir Dis 2010;4(3):177-85
24. Riordan JR, Rommens JM, Kerem B, et al. Identification of the cystic fibrosis gene: Cloning and characterization of complementary DNA. Science 1989;245(4922):1066-73. First report of cDNA of CF gene. (Pubitemid 19231814)
25. Drug Development Pipeline. Available from: Http://www.cff.org/research/ DrugDevelopmentPipeline [Last accessed 12 April 2010] Developmental status of new therapeutic agents for CF patients.
26. Cystic Fibrosis Patient Registry Annual Data Report 2008 Available from: Http://www.cff.org/UploadedFiles/ research/ClinicalResearch/ 2008-Patient-Registry-Report.pdf [Last accessed 18 October 2010]
27. Doring G, Conway S, Heijerman H, et al. Antibiotic therapy against Pseudomonas aeruginosa in cystic fibrosis: A European consensus. Eur Respir J 2000;16(4):749-67
28. Moss RB. Allergic bronchopulmonary aspergillosis and Aspergillus infection in cystic fibrosis. Curr Opin Pulm Med 2010;16(6):598-603
29. Proesmans M, Vermeulen F, De Boeck K. What's new in cystic fibrosis? From treating symptoms to correction of the basic defect. Eur J Pediatr 2008;167(8):839-49
30. Flume PA, O'Sullivan BP, Robinson KA, et al. Cystic fibrosis pulmonary guidelines: Chronic medications for maintenance of lung health. Am J Respir Crit Care Med 2007;176(10):957-69 (Pubitemid 350127838)
31. Clement A, Tamalet A, Leroux E, et al. Long term effects of azithromycin in patients with cystic fibrosis: A double blind, placebo controlled trial. Thorax 2006;61(10):895-902 (Pubitemid 44570311)
32. Equi A, Balfour-Lynn IM, Bush A, et al. Long term azithromycin in children with cystic fibrosis: A randomised, placebo-controlled crossover trial. Lancet 2002;360(9338):978-84 (Pubitemid 35284109)
33. Saiman L, Marshall BC, Mayer-Hamblett N, et al. Azithromycin in patients with cystic fibrosis chronically infected with pseudomonas aeruginosa: A randomized controlled trial. JAMA 2003;290(13):1749-56 (Pubitemid 37430625)
34. Wolter J, Seeney S, Bell S, et al. Effect of long term treatment with azithromycin on disease parameters in cystic fibrosis: A randomised trial. Thorax 2002;57:212-16 (Pubitemid 34214405)
35. Friedlander AL, Albert RK. Chronic macrolide therapy in inflammatory airways diseases. Chest 2010;138(5):1202-12
36. Ribeiro CMP, Hurd H, Wu Y, et al. Azithromycin treatment alters gene expression in inflammatory, lipid metabolism, and cell cycle pathways in well-differentiated human airway epithelia. PLoS ONE 2009;4(6):e5806
37. Kanoh S, Rubin BK. Mechanisms of action and clinical application of macrolides as immunomodulatory medications. Clin Microbiol Rev 2010;23(3):590-615
38. Shinkai M, Lopez-Boado YS, Rubin BK. Clarithromycin has an immunomodulatory effect on ERK-mediated inflammation induced by Pseudomonas aeruginosa flagellin. J Antimicrob Chemother 2007;59(6):1096-101 (Pubitemid 47073319)
39. Cigana C, Nicolis E, Pasetto M, et al. Anti-inflammatory effects of azithromycin in cystic fibrosis airway epithelial cells. Biochem Biophys Res Commun 2006;350(4):977-82 (Pubitemid 44584188)
40. Walker TS, Tomlin KL, Worthen GS, et al. Enhanced Pseudomonas aeruginosa biofilm development mediated by human neutrophils. Infect Immun 2005;73(6):3693-701 (Pubitemid 40745914)
41. Tomkiewicz R, Kishore C, Freeman J, et al. DNA and actin filament ultrastructure in cystic fibrosis sputum. In: Baum G, Priel Z, Roth Y, Liron N, Ostield E, editors, Cilia, mucus, and mucociliary interactions. Marcel Dekker, Inc., New York; 1998. p. 333-41
42. Sheils CA, Kas J, Travassos W, et al. Actin filaments mediate DNA fiber formation in chronic inflammatory airway disease. Am J Pathol 1996;148(3):919-27 (Pubitemid 126660683)
43. Parks Q, Young R, Poch K, et al. Neutrophil enhancement of Pseudomonas aeruginosa biofilm development: Human F-actin and DNA as targets for therapy. J Med Microbiol 2009;58(Pt 4):492-502
44. Broughton-Head VJ, Shur J, Carroll MP, et al. Unfractionated heparin reduces the elasticity of sputum from patients with cystic fibrosis. Am J Physiol Lung Cell Mol Physiol 2007;293(5):L1240-9 (Pubitemid 350159408)
45. Flume PA, Mogayzel PJ Jr, Robinson KA, et al. Cystic fibrosis pulmonary guidelines: Pulmonary complications: Hemoptysis and pneumothorax. Am J Respir Crit Care Med 2010;182(3):298-306
46. Flume PA, Yankaskas JR, Ebeling M, et al. Massive hemoptysis in cystic fibrosis. Chest 2005;128(2):729-38 (Pubitemid 41140503)
47. Shur J, Nevell TG, Ewen RJ, et al. Cospray-dried unfractionated heparin with L-leucine as a dry powder inhaler mucolytic for cystic fibrosis therapy. J Pharm Sci 2008;97(11):4857-68
48. Nilsson H, Dragomir A, Ahlander A, et al. Effects of hyperosmotic stress on cultured airway epithelial cells. Cell Tissue Res 2007;330(2):257-69 (Pubitemid 47512594)
49. Donaldson SH, Bennett WD, Zeman KL, et al. Mucus clearance and lung function in cystic fibrosis with hypertonic saline. N Engl J Med 2006;354(3):241-50 (Pubitemid 43113029)
50. Hirsh AJ. Altering airway surface liquid volume: Inhalation therapy with amiloride and hyperosmotic agents. Adv Drug Deliv Rev 2002;54(11):1445-62 (Pubitemid 35378659)
51. Elkins MR, Robinson M, Rose BR, et al. A controlled trial of long-term inhaled hypertonic saline in patients with cystic fibrosis. N Engl J Med 2006;354(3):229-40 (Pubitemid 43113028)
52. Elkins MR, Bye PT. Inhaled hypertonic saline as a therapy for cystic fibrosis. Curr Opin Pulm Med 2006;12(6):445-52 (Pubitemid 44624606)
53. Eng PA, Morton J, Douglass JA, et al. Short-term efficacy of ultrasonically nebulized hypertonic saline in cystic fibrosis. Pediatr Pulmonol 1996;21(2):77-83 (Pubitemid 26098513)
54. Daviskas E, Anderson Sandra D, Eberl S, et al. Inhalation of dry powder mannitol improves clearance of mucus in patients with bronchiectasis. Am J Respir Crit Care Med 1999;159(6):1843-8 (Pubitemid 29275053)
55. Jaques A, Daviskas E, Turton JA, et al. Inhaled mannitol improves lung function in cystic fibrosis. Chest 2008;133(6):1388-96 (Pubitemid 351892995)
56. Daviskas E, Anderson SD, Eberl S, et al. Effect of increasing doses of mannitol on mucus clearance in patients with bronchiectasis. Eur Respir J 2008;3(1):765-72
57. Wills PJ. Inhaled mannitol in cystic fibrosis. Expert Opin Investig Drugs 2007;16(7):1121-6 (Pubitemid 47074166)
58. Robinson M, Daviskas E, Eberl S, et al. The effect of inhaled mannitol on bronchial mucus clearance in cystic fibrosis patients: A pilot study. Eur Respir J 1999;14(3):678-85 (Pubitemid 29479736)
59. Sloane PA, Rowe SM. Cystic fibrosis transmembrane conductance regulator protein repair as a therapeutic strategy in cystic fibrosis. Curr Opin Pulm Med 2010;16(6):591-7
60. Amaral M, Kunzelmann K. Molecular targeting of CFTR as a therapeutic approach to cystic fibrosis. Trends Pharmacol Sci 2007;28(9):334, 447. Overview of CF disease and CFTR-targeted therapy.
61. Kellerman D, Rossi Mospan A, Engels J, et al. Denufosol: A review of studies with inhaled P2Y2 agonists that led to phase 3. Pulm Pharmacol Ther 2008;21(4):600-7 (Pubitemid 351970709)
62. Kellerman D, Evans R, Mathews D, et al. Inhaled P2Y(2) receptor agonists as a treatment for patients with cystic fibrosis lung disease. Adv Drug Deliv Rev 2002;54(11):1463-74 (Pubitemid 35375770)
63. Van Goor F, Hadida S, Grootenhuis PDJ, et al. Rescue of CF airway epithelial cell function in vitro by a CFTR potentiator, VX-770. Proc Natl Acad Sci 2009;106(44):18825-30
64. Accurso FJ, Rowe SM, Clancy JP, et al. Effect of VX-770 in persons with cystic fibrosis and the G551D-CFTR mutation. N Engl J Med 2010;363(21):1991- 2003. Phase II trial of VX-770, a CFTR potentiator.
65. Sermet-Gaudelus I, Boeck KD, Casimir GJ, et al. Ataluren (PTC124) induces cystic fibrosis transmembrane conductance regulator protein expression and activity in children with nonsense mutation cystic fibrosis. Am J Respir Crit Care Med 2010;182(10):1262-72. Phase II trial of PTC124, a drug for CF patients with nonsense mutations.
66. Available from: Http://clinicaltrials.gov/ ct2/show/NCT01117012 [Last accessed 12 April 2010]
67. Available from: Http://clinicaltrials.gov/ ct2/show/NCT00803205 [Last accessed 12 April 2010]
68. Griesenbach U, Alton EW. Gene transfer to the lung: Lessons learned from more than 2 decades of CF gene therapy. Adv Drug Deliv Rev 2009;61(2):128-39. Detailed review of CF gene therapy.
69. Boucher RC. Status of gene therapy for cystic fibrosis lung disease. J Clin Invest 1999;103(4):441-5 (Pubitemid 29094042)
70. Atkinson TJ. Cystic fibrosis, vector-mediated gene therapy, and relevance of toll-like receptors: A review of problems, progress, and possibilities. Curr Gene Ther 2008;8(3):201-7
71. Boyd AC. Gene and stem cell therapy. In: Bush A, Alton EWFW, Davies JC, Griesenbach U, Jaffe A, editors, Progress in respiratory research: Cystic fibrosis in the 21st Century, Karger, Basel; 2006. Vol. 34, pp. 221-9
72. Teichler Zallen D. US gene therapy in crisis. Trends Genet 2000;16(6):272-5
73. Raper SE, Chirmule N, Lee FS, et al. Fatal systemic inflammatory response syndrome in a ornithine transcarbamylase deficient patient following adenoviral gene transfer. Mol Genet Metab 2003;80(1-2):148-58 (Pubitemid 37272241)
74. Alexander BL, Ali RR, Alton EWF, et al. Progress and prospects: Gene therapy clinical trials (part 1). Gene Ther 2007;14(20):1439-47
75. Knowles MR, Hohneker KW, Zhou Z, et al. A controlled study of adenoviral-vector-mediated gene transfer in the nasal epithelium of patients with cystic fibrosis. N Engl J Med 1995;333(13):823-31
76. Zuckerman JB, Robinson CB, MacCoy KS, et al. A phase I study of adenovirus-mediated transfer of the human cystic fibrosis transmembrane conductance regulator gene to a lung segment of individuals with cystic fibrosis. Hum Gene Ther 1999;10(18):2973-85
77. Zabner J, Ramsey BW, Meeker DP, et al. Repeat administration of an adenovirus vector encoding cystic fibrosis transmembrane conductance regulator to the nasal epithelium of patients with cystic fibrosis. J Clin Invest 1996;97(6):1504-11 (Pubitemid 26097041)
78. Flotte TR, Zeitlin PL, Reynolds TC, et al. Phase I trial of intranasal and endobronchial administration of a recombinant adeno-associated virus serotype 2 (rAAV2)-CFTR vector in adult cystic fibrosis patients: A two-part clinical study. Hum Gene Ther 2003;14(11):1079-88 (Pubitemid 36851399)
79. Aitken ML, Moss RB, Waltz DA, et al. A phase I study of aerosolized administration of tgAAVCF to cystic fibrosis subjects with mild lung disease. Hum Gene Ther 2001;12(15):1907-16 (Pubitemid 32947233)
80. Barnes PJ. Nuclear factor-[kappa]B. Int J Biochem Cell Biol 1997;29(6):867-70
81. Lambert G, Becker B, Schreiber R, et al. Control of cystic fibrosis transmembrane conductance regulator expression by BAP31. J Biol Chem 2001;276(23):20340-5 (Pubitemid 37411113)
82. Mall M, Grubb BR, Harkema JR, et al. Increased airway epithelial Na+ absorption produces cystic fibrosis-like lung disease in mice. Nat Med 2004;10(5):487-93 (Pubitemid 38667907)
83. Vij N, Fang S, Zeitlin PL. Selective inhibition of endoplasmic reticulum-associated degradation rescues DF508-cystic fibrosis transmembrane regulator and suppresses interleukin-8 levels. J Biol Chem 2006;281(25):17369-78
84. Gary DJ, Puri N, Won Y-Y. Polymer-based siRNA delivery: Perspectives on the fundamental and phenomenological distinctions from polymer-based DNA delivery. J Control Release 2007;121(1-2):64-73 (Pubitemid 47126065)
85. Durcan N, Murphy C, Cryan S-A. Inhalable siRNA: Potential as a therapeutic agent in the lungs. Mol Pharm 2008;5(4):559-66
86. Mok H, Lee SH, Park JW, et al. Multimeric small interfering ribonucleic acid for highly efficient sequence-specific gene silencing. Nat Mater 2010;9(3):272-8
87. Bolcato-Bellemin A-L, Bonnet M-E, Creusat Gl, et al. Sticky overhangs enhance siRNA-mediated gene silencing. Proc Natl Acad Sci USA 2007;104(41):16050-5 (Pubitemid 350099361)
88. Lee S-Y, Huh MS, Lee S, et al. Stability and cellular uptake of polymerized siRNA (poly-siRNA)/polyethylenimine (PEI) complexes for efficient gene silencing. J Control Release 2010;141(3):339-46
89. Available from: Http://clinicaltrials.gov/ ct2/show/NCT00645788 [Last accessed 12 April 2010]
90. Available from: Http://clinicaltrials.gov/ ct2/show/NCT00910351 [Last accessed 12 April 2010]
91. Crowther Labiris NR, Holbrook AM, Chrystyn H, et al. Dry powder versus intravenous and nebulized gentamicin in cystic fibrosis and bronchiectasis. A Pilot Study. Am J Respir Crit Care Med 1999;160(5):1711-16
92. Konstan MW, Flume PA, Kappler M, et al. Safety, efficacy and convenience of tobramycin inhalation powder in cystic fibrosis patients: The EAGER trial. J Cystic Fibrosis 2011;10(1):54-61. Phase III clinical trial of tobramycin inhalation powder in CF patients.
93. Geller DE, Konstan MW, Noonberg SB, et al. Novel tobramycin inhalation powder in cystic fibrosis subjects: Pharmacokinetics and safety. Pediatr Pulmonol 2007;42(4):307-13 (Pubitemid 46608898)
94. Pilcer GVF, Amighi K. Preparation and characterization of spray-dried tobramycin powders containing nanoparticles for pulmonary delivery. Int J Pharm 2009;365(1-2):162-9
95. Le Brun PPH, de Boer AH, Mannes GPM, et al. Dry powder inhalation of antibiotics in cystic fibrosis therapy: Part 2 Inhalation of a novel colistin dry powder formulation: A feasibility study in healthy volunteers and patients. Eur J Pharm Biopharm 2002;54(1):25-32 (Pubitemid 34663853)
96. de Boer AH, Le Brun PPH, van der Woude HG, et al. Dry powder inhalation of antibiotics in cystic fibrosis therapy, part 1: Development of a powder formulation with colistin sulfate for a special test inhaler with an air classifier as de-agglomeration principle. Eur J Pharm Biopharm 2002;54(1):17-24 (Pubitemid 34663852)
97. Westerman EM, de Boer AH, Le Brun PPH, et al. Dry powder inhalation of colistin sulphomethate in healthy volunteers: A pilot study. Int J Pharm 2007;335(1-2):41-5 (Pubitemid 46482863)
98. Son Y-J, McConville JT. Advancements in dry powder delivery to the lung. Drug Dev Ind Pharm 2008;34(9):948-59. A review of dry powder inhaler devices.
99. Newman SP. Dry powder inhalers for optimal drug delivery. Expert Opin Biol Ther 2004;4(1):23-33 (Pubitemid 38057264)
100. Islam N, Gladki E. Dry powder inhalers (DPIs)-A review of device reliability and innovation. Int J Pharm 2008;360(1-2):1-11
101. Atkins PJ. Dry powder inhalers: An overview. Respir Care 2005;50(10):1304-12, discussion 1312 (Pubitemid 46173313)
102. Prime D, Atkins PJ, Slater A, et al. Review of dry powder inhalers. Adv Drug Deliv Rev 1997;26(1):51-8 (Pubitemid 27288484)
103. Geller DE. Comparing clinical features of the nebulizer, metered-dose inhaler, and dry powder inhaler. Respir Care 2005;50(10):1313-21. Comparison of inhaler devices. (Pubitemid 46173315)
104. Dalby R, Spallek M, Voshaar T. A review of the development of Respimat® Soft Mist(TM) Inhaler. Int J Pharm 2004;283(1-2):1-9 (Pubitemid 39200921)
105. Watts AB, McConville JT, Williams RO. Current therapies and technological advances in aqueous aerosol drug delivery. Drug Dev Ind Pharm 2008;34(9):913-22
106. Berger W. Aerosol devices and asthma therapy. Curr Drug Deliv 2009;6(1):38-49
107. Geller DE, Kesser KC. The I-neb adaptive aerosol delivery system enhances delivery of alpha1-antitrypsin with controlled inhalation. J Aerosol Med Pulm Drug Deliv 2010;23(s1):S-55-9
108. Kesser KC, Geller DE. New aerosol delivery devices for cystic fibrosis. Respir Care 2009;54(6):754-67, discussion 767-8
109. Hanes J, Demeester J. Drug and gene delivery to mucosal tissues: The mucus barrier. Adv Drug Deliv Rev 2009;61(2):73-4
110. Sanders N, Rudolph C, Braeckmans K, et al. Extracellular barriers in respiratory gene therapy. Adv Drug Deliv Rev 2009;61(2):115-27. Comprehensive review of barrier properties of respiratory mucus and alveolar fluid towards respiratory gene delivery.
111. Cone RA. Barrier properties of mucus. Adv Drug Deliv Rev 2009;61(2):75-85. Comprehensive review of physical properties of mucus and its barrier functions to nanoparticulate drug delivery.
112. Lai SK, Wang Y-Y, Wirtz D, et al. Micro- and macrorheology of mucus. Adv Drug Deliv Rev 2009;61(2):86-100. Comprehensive review of rheological properties of mucus.
113. Patton JS. Mechanisms of macromolecule absorption by the lungs. Adv Drug Deliv Rev 1996;19(1):3-36 (Pubitemid 26167852)
114. Wine JJ. The genesis of cystic fibrosis lung disease. J Clin Invest 1999;103(3):309-12 (Pubitemid 29069979)
115. Cu Y, Saltzman WM. Mathematical modeling of molecular diffusion through mucus. Adv Drug Deliv Rev 2009;61(2):101-14
116. Bansil R, Stanley E, Lamont JT. Mucin biophysics. Annu Rev Physiol 1995;57(1):635-57
117. Thornton DJ, Sheehan JK. From mucins to mucus: Toward a more coherent understanding of this essential barrier. Proc Am Thorac Soc 2004;1(1):54-61
118. Mrsny RJ. Lessons from nature: 'Pathogen-Mimetic' systems for mucosal Nano-medicines. Adv Drug Deliv Rev 2009;61(2):172-92
119. Voynow JA, Rubin BK. Mucins, mucus, and sputum. Chest 2009;135(2):505-12
120. Lai SK, Wang Y-Y, Hida K, et al. Nanoparticles reveal that human cervicovaginal mucus is riddled with pores larger than viruses. Proc Natl Acad Sci 2010;107(2):598-603
121. Yudin AI, Hanson FW, Katz DF. Human cervical mucus and its interaction with sperm: A fine-structural view. Biol Reprod 1989;40(3):661-71 (Pubitemid 19149772)
122. Psychoyos A, Borg V, Cohen J, et al. Human cervical mucus during the menstrual cycle and pregnancy in normal and pathological conditions. J Reprod Med 1975;14(5):192-6
123. Suk JS, Lai SK, Wang Y-Y, et al. The penetration of fresh undiluted sputum expectorated by cystic fibrosis patients by non-adhesive polymer nanoparticles. Biomaterials 2009;30(13):2591-7. Demonstrates the ability of surface-protected nanoparticles to penetrate CF mucus.
124. Broughton-Head VJV, Smith JRJ, Shur JJ, et al. Actin limits enhancement of nanoparticle diffusion through cystic fibrosis sputum by mucolytics. Pulm Pharmacol Ther 2007;20(6):708-17
125. Dawson M, Wirtz D, Hanes J. Enhanced viscoelasticity of human cystic fibrotic sputum correlates with increasing microheterogeneity in particle transport. J Biol Chem 2003;278(50):50393-401 (Pubitemid 37548883)
126. Lai SK, Wang Y-Y, Cone R, et al. Altering mucus rheology to 'Solidify' human mucus at the nanoscale. PLoS ONE 2009;4(1):e4294
127. Olmsted SS, Padgett JL, Yudin AI, et al. Diffusion of macromolecules and virus-like particles in human cervical mucus. Biophys J 2001;81(4):1930-7 (Pubitemid 32917145)
128. Perricone MA, Rees DD, Sacks CR, et al. Inhibitory effect of cystic fibrosis sputum on adenovirus mediated gene transfer in cultured epithelial cells. Hum Gene Ther 2000;11(14):1997-2008
129. Sanders NN, Van Rompaey E, De Smedt SC, et al. Structural alterations of gene complexes by cystic fibrosis sputum. Am J Respir Crit Care Med 2001;164(3):486-93 (Pubitemid 32778221)
130. Davies JC, Bilton D. Bugs, biofilms, and resistance in cystic fibrosis. Respir Care 2009;54(5):628-40
131. Hoiby N, Bjarnsholt T, Givskov M, et al. Antibiotic resistance of bacterial biofilms. Int J Antimicrob Agents 2010;35(4):322-32
132. Yeates DB, Aspin N, Levison H, et al. Mucociliary tracheal transport rates in man. J Appl Physiol 1975;39(3):487-95
133. Suarez S, Hickey AJ. Drug properties affecting aerosol behavior. Respir Care 2000;45(6):652-66 (Pubitemid 30484805)
134. Mall MA. Role of cilia, mucus, and airway surface liquid in mucociliary dysfunction: Lessons from mouse models. J Aerosol Med Pulm Drug Deliv 2008;21(1):13-24
135. Sinn PL, Shah AJ, Donovan MD, et al. Viscoelastic gel formulations enhance airway epithelial gene transfer with viral vectors. Am J Respir Cell Mol Biol 2005;32(5):404-10 (Pubitemid 40629325)
136. Deneuville E, Perrot-Minot C, Pennaforte F, et al. Revisited physicochemical and transport properties of respiratory mucus in genotyped cystic fibrosis patients. Am J Respir Crit Care Med 1997;156(1):166-72 (Pubitemid 27293183)
137. King M. The role of mucus viscoelasticity in cough clearance. Biorheology 1987;24(6):589-97 (Pubitemid 18021584)
138. Aronoff SC. Outer membrane permeability in Pseudomonas cepacia: Diminished porin content in a beta-lactam-resistant mutant and in resistant cystic fibrosis isolates. Antimicrob Agents Chemother 1988;32(11):1636-9 (Pubitemid 18267607)
139. Nicas TI, Hancock RE. Pseudomonas aeruginosa outer membrane permeability: Isolation of a porin protein F-deficient mutant. J Bacteriol 1983;153(1):281-5 (Pubitemid 13119866)
140. Burns JL, Hedin LA, Lien DM. Chloramphenicol resistance in Pseudomonas cepacia because of decreased permeability. Antimicrob Agents Chemother 1989;33(2):136-41 (Pubitemid 19053846)
141. Burns JL, Clark DK. Salicylate-inducible antibiotic resistance in Pseudomonas cepacia associated with absence of a pore-forming outer membrane protein. Antimicrob Agents Chemother 1992;36(10):2280-5
142. Nikaido H. Prevention of drug access to bacterial targets: Permeability barriers and active efflux. Science 1994;264(5157):382-8 (Pubitemid 24178901)
143. Dostal RE, Seale JP, Yan BJ. Resistance to ciprofloxacin of respiratory pathogens in patients with cystic fibrosis. Med J Austr 1992;156(1):20-4
144. Watkins J, Francis J, Kuzemko JA. Does monotherapy of pulmonary infections in cystic fibrosis lead to early development of resistant strains of Pseudomonas aeruginosa? Scand J Gastroenterol 1988;143:81-5
145. Cheer SM, Waugh J, Noble S. Inhaled tobramycin (TOBI): A review of its use in the management of Pseudomonas aeruginosa infections in patients with cystic fibrosis. Drugs 2003;63(22):2501-20 (Pubitemid 37392915)
146. Smith AL, Ramsey BW, Hedges DL, et al. Safety of aerosol tobramycin administration for 3 months to patients with cystic fibrosis. Pediatr Pulmonol 1989;7(4):265-71
147. Burns JL, Van Dalfsen JM, Shawar RM, et al. Effect of chronic intermittent administration of inhaled tobramycin on respiratory microbial flora in patients with cystic fibrosis. J Infect Dis 1999;179(5):1190-6 (Pubitemid 29196500)
148. Prober CG, Walson PD, Jones J. Technical report: Precautions regarding the use of aerosolized antibiotics. Committee on Infectious Diseases and Committee on Drugs. Pediatrics 2000;106(6):E89
149. Tsifansky MD, Yeo Y, Evgenov OV, et al. Microparticles for inhalational delivery of antipseudomonal antibiotics. AAPS J 2008;10(2):254-60
150. Adi H, Young PM, Chan H-K, et al. Controlled release antibiotics for dry powder lung delivery. Drug Dev Ind Pharm 2010;36(1):119-26
151. Adi H, Young PM, Chan HK, et al. Cospray dried antibiotics for dry powder lung delivery. J Pharm Sci 2008;97(8):3356-66
152. Fish DN, Choi MK, Jung R. Synergic activity of cephalosporins plus fluoroquinolones against Pseudomonas aeruginosa with resistance to one or both drugs. J Antimicrob Chemother 2002;50(6):1045-9 (Pubitemid 36032829)
153. Pickles RJ, Fahrner JA, Petrella JM, et al. Retargeting the coxsackievirus and adenovirus receptor to the apical surface of polarized epithelial cells reveals the glycocalyx as a barrier to adenovirus-mediated gene transfer. J Virol 2000;74(13):6050-7 (Pubitemid 30412976)
154. Walters RW, Grunst T, Bergelson JM, et al. Basolateral localization of fiber receptors limits adenovirus infection from the apical surface of airway epithelia. J Biol Chem 1999;274(15):10219-26
155. Harvey B-G, Leopold PL, Hackett NR, et al. Airway epithelial CFTR mRNA expression in cystic fibrosis patients after repetitive administration of a recombinant adenovirus. J Clin Invest 1999;104(9):1245-55 (Pubitemid 29536295)
156. Moss RB, Milla C, Colombo J, et al. Repeated aerosolized AAV-CFTR for treatment of cystic fibrosis: A randomized placebo-controlled phase 2B trial. Hum Gene Ther 2007;18(8):726-32 (Pubitemid 47378069)
157. Sinn PL, Burnight ER, McCray PB. Progress and prospects: Prospects of repeated pulmonary administration of viral vectors. Gene Ther 2009;16(9):1059-65
158. Dean DA, Strong DD, Zimmer WE. Nuclear entry of nonviral vectors. Gene Ther 2005;12(11):881-90 (Pubitemid 40852206)
159. Lechardeur D, Sohn KJ, Haardt M, et al. Metabolic instability of plasmid DNA in the cytosol: A potential barrier to gene transfer. Gene Ther 1999;6(4):482-97 (Pubitemid 29192657)
160. Pollard H, Toumaniantz G, Amos JL, et al. Ca2+-sensitive cytosolic nucleases prevent efficient delivery to the nucleus of injected plasmids. J Gene Med 2001;3(2):153-64 (Pubitemid 33685442)
161. Lam AP, Dean DA. Progress and prospects: Nuclear import of nonviral vectors. Gene Ther 2010;17(4):439-47
162. Chowdhury EH. Nuclear targeting of viral and non-viral DNA. Expert Opin Drug Deliv 2009;6(7):697-703
163. Viola JR, El-Andaloussi S, Oprea II, et al. Non-viral nanovectors for gene delivery: Factors that govern successful therapeutics. Expert Opin Drug Deliv 2010;7(6):721-35
164. Minchin RF, Yang S. Endosomal disruptors in non-viral gene delivery. Expert Opin Drug Deliv 2010;7(3):331-9
165. Xu P, Quick G, Yeo Y. Gene delivery through the use of a hyaluronate-associated intracellularly degradable cross-linked polyethyleneimine. Biomaterials 2009;30(29):5834-43
166. Mugabe C, Azghani AO, Omri A. Liposome-mediated gentamicin delivery: Development and activity against resistant strains of Pseudomonas aeruginosa isolated from cystic fibrosis patients. J Antimicrob Chemother 2005;55(2):269-71 (Pubitemid 40331158)
167. Rukholm G, Mugabe C, Azghani AO, et al. Antibacterial activity of liposomal gentamicin against Pseudomonas aeruginosa: A time-kill study. Int J Antimicrob Agents 2006;27(3):247-52 (Pubitemid 43246956)
168. Beaulac C, Sachetelli S, Lagace J. In-vitro bactericidal efficacy of sub-MIC concentrations of liposome-encapsulated antibiotic against gram-negative and gram-positive bacteria. J Antimicrob Chemother 1998;41(1):35-41 (Pubitemid 28064248)
169. Beaulac C, Sachetelli S, Lagace J. In vitro bactericidal evaluation of a low phase transition temperature liposomal tobramycin formulation as a dry powder preparation against gram negative and gram positive bacteria. J Liposome Res 1999;9(3):301-12 (Pubitemid 29439397)
170. Halwani M, Mugabe C, Azghani AO, et al. Bactericidal efficacy of liposomal aminoglycosides against Burkholderia cenocepacia. J Antimicrob Chemother 2007;60(4):760-9 (Pubitemid 47434253)
171. Alipour M, Suntres ZE, Halwani M, et al. Activity and interactions of liposomal antibiotics in presence of polyanions and sputum of patients with cystic fibrosis. PLoS ONE 2009;4(5):e5724
172. Demaeyer P, Akodad EM, Gravet E, et al. Disposition of liposomal gentamicin following intrabronchial administration in rabbits. J Microencapsul 1993;10(1):77-88 (Pubitemid 23069816)
173. Omri A, Beaulac C, Bouhajib M, et al. Pulmonary retention of free and liposome-encapsulated tobramycin after intratracheal administration in uninfected rats and rats infected with Pseudomonas aeruginosa. Antimicrob Agents Chemother 1994;38(5):1090-5 (Pubitemid 24150843)
174. Marier JF, Lavigne J, Ducharme MP. Pharmacokinetics and efficacies of liposomal and conventional formulations of tobramycin after intratracheal administration in rats with pulmonary Burkholderia cepacia infection. Antimicrob Agents Chemother 2002;46(12):3776-81 (Pubitemid 35403251)
175. Meers P, Neville M, Malinin V, et al. Biofilm penetration, triggered release and in vivo activity of inhaled liposomal amikacin in chronic Pseudomonas aeruginosa lung infections. J Antimicrob Chemother 2008;61(4):859-68. Demonstrates in vitro biofilm penetration and in vivo antibacterial effect of liposomal amikacin. (Pubitemid 351426071)
176. Beaulac C, Clement-Major S, Hawari J, et al. Eradication of mucoid Pseudomonas aeruginosa with fluid liposome-encapsulated tobramycin in an animal model of chronic pulmonary infection. Antimicrob Agents Chemother 1996;40(3):665-9
177. Dames P, Gleich B, Flemmer A, et al. Targeted delivery of magnetic aerosol droplets to the lung. Nat Nano 2007;2(8):495-9. Demonstrates that magnetic forces can be used to improve nanoparticle delivery to the lungs. (Pubitemid 47220067)
178. Sanders NN, Van Rompaey E, De Smedt SC, et al. On the transport of lipoplexes through cystic fibrosis sputum. Pharm Res 2002;19(4):451-6 (Pubitemid 34408944)
179. Kushwah R, Oliver JR, Cao H, et al. Nacystelyn enhances adenoviral vector-mediated gene delivery to mouse airways. Gene Ther 2007;14(16):1243-8 (Pubitemid 47215426)
180. Ferrari S, Kitson C, Farley R, et al. Mucus altering agents as adjuncts for nonviral gene transfer to airway epithelium. Gene Ther 2001;8(18):1380-6 (Pubitemid 32895668)
181. Lai SK, O'Hanlon DE, Harrold S, et al. Rapid transport of large polymeric nanoparticles in fresh undiluted human mucus. Proc Natl Acad Sci USA 2007;104(5):1482-7. Demonstrates the ability of surface-protected nanoparticles to penetrate cervicovaginal mucus. (Pubitemid 46214616)
182. Lai SK, Wang Y-Y, Hanes J. Mucus-penetrating nanoparticles for drug and gene delivery to mucosal tissues. Adv Drug Deliv Rev 2009;61(2):158-71. Review of surfaceprotected nanoparticles.
183. Tang BC, Dawson M, Lai SK, et al. Biodegradable polymer nanoparticles that rapidly penetrate the human mucus barrier. Proc Natl Acad Sci USA 2009;106(46):19268-73
184. Wang YY, Lai SK, Suk JS, et al. Addressing the PEG mucoadhesivity paradox to engineer nanoparticles that 'Slip' through the human mucus barrier. Angew Chem Int Ed 2008;47(50):9726-9
185. Sanders NN, De Smedt SC, Demeester J. Mobility and stability of gene complexes in biogels. J Control Release 2003;87(1-3):117-29 (Pubitemid 36255449)
186. Sanders NN, De Smedt SC, Cheng SH, et al. Pegylated GL67 lipoplexes retain their gene transfection activity after exposure to components of CF mucus. Gene Ther 2002;9(6):363-71 (Pubitemid 34414034)
187. Vij N, Min T, Marasigan R, et al. Development of PEGylated PLGA nanoparticle for controlled and sustained drug delivery in cystic fibrosis. J Nanobiotechnol 2010;8(1):22
188. Mishra S, Webster P, Davis ME. PEGylation significantly affects cellular uptake and intracellular trafficking of non-viral gene delivery particles. Eur J Cell Biol 2004;83(3):97-111 (Pubitemid 38765217)
189. Gryparis EC, Hatziapostolou M, Papadimitriou E, et al. Anticancer activity of cisplatin-loaded PLGA-mPEG nanoparticles on LNCaP prostate cancer cells. Eur J Pharm Biopharm 2007;67(1):1-8 (Pubitemid 46991325)
190. Romberg B, Hennink W, Storm G. Sheddable coatings for long-circulating nanoparticles. Pharm Res 2008;25(1):55-71
191. Hong RL, Huang CJ, Tseng YL, et al. Direct comparison of liposomal doxorubicin with or without polyethylene glycol coating in C-26 tumor-bearing mice: Is surface coating with polyethylene glycol beneficial? Clin Cancer Res 1999;5(11):3645-52
192. Kaasgaard T, Mouritsen OG, Jorgensen K. Screening effect of PEG on avidin binding to liposome surface receptors. Int J Pharm 2001;214(1-2):63-5 (Pubitemid 32244079)
193. Hatakeyama H, Akita H, Kogure K, et al. Development of a novel systemic gene delivery system for cancer therapy with a tumor-specific cleavable PEG-lipid. Gene Ther 2007;14(1):68-77 (Pubitemid 44942867)
194. Buyens K, Lucas B, Raemdonck K, et al. A fast and sensitive method for measuring the integrity of siRNA-carrier complexes in full human serum. J Control Release 2008;126(1):67-76
195. Ito T, Iida-Tanaka N, Niidome T, et al. Hyaluronic acid and its derivative as a multi-functional gene expression enhancer: Protection from non-specific interactions, adhesion to targeted cells, and transcriptional activation. J Control Release 2006;112(3):382-8 (Pubitemid 43737143)
196. Jiang G, Min S, Kim M, et al. Alginate/ PEI/DNA polyplexes: A new gene delivery system. Yao Xue Xue Bao 2006;41(5):439-45 (Pubitemid 44022669)
197. Cheung CY, Murthy N, Stayton PS, et al. A pH-sensitive polymer that enhances cationic lipid-mediated gene transfer. Bioconjug Chem 2001;12(6):906-10 (Pubitemid 33136860)
198. Garcia-Contreras L, Hickey AJ. Pharmaceutical and biotechnological aerosols for cystic fibrosis therapy. Adv Drug Deliv Rev 2002;54(11):1491-504 (Pubitemid 35375772)
199. Alipour M, Suntres ZE, Omri A. Importance of DNase and alginate lyase for enhancing free and liposome encapsulated aminoglycoside activity against Pseudomonas aeruginosa. J Antimicrob Chemother 2009;64(2):317-25
200. Yang Y, Tsifansky MD, Wu C-J, et al. Inhalable antibiotic delivery using a dry powder co-delivering recombinant deoxyribonuclease and ciprofloxacin for treatment of cystic fibrosis. Pharm Res 2010;27(1):151-60
201. Yang Y, Tsifansky MD, Shin S, et al. Mannitol-guided delivery of ciprofloxacin in artificial cystic fibrosis mucus model. Biotechnol Bioeng. Available from: Http://onlinelibrary.wiley.com/ doi/10.1002/bit.23046/pdf 15 Jan 2011. [Epub ahead of print]
202. Adi H, Young PM, Chan H-K, et al. Co-spray dried mannitol-ciprofloxacin dry powder inhaler for cystic fibrosis and chronic obstructive pulmonary disease. Eur J Pharm Sci 2010;40:239-47
203. McGill SL, Smyth HDC. Disruption of the mucus barrier by topically applied exogenous particles. Mol Pharm 2010;7(6):2280-8
204. Chen EYT, Wang Y-C, Chen C-S, et al. Functionalized positive nanoparticles reduce mucin swelling and dispersion. PLoS ONE 2010;5(11):e15434
205. Dorin JR. Animal models. In: Bush A, EWA, Davies JC, Griesenbach U, Jaffe A, editors, Progress in respiratory research: Cystic fibrosis in the 21st century. Karger, Basel; 2006. p. 84-92. A good review of animal model development for CF research.
206. Clarke LL, Grubb BR, Yankaskas JR, et al. Relationship of a non-cystic fibrosis transmembrane conductance regulatormediated chloride conductance to organ-level disease in Cftr(-/-) mice. Proc Natl Acad Sci USA 1994;91(2):479-83
207. Cash HA, Woods DE, McCullough B, et al. A rat model of chronic respiratory infection with Pseudomonas aeruginosa. Am Rev Respir Dis 1979;119(3):453-9 (Pubitemid 9131392)
208. Kukavica-Ibrulj I, Levesque RC. Animal models of chronic lung infection with Pseudomonas aeruginosa: Useful tools for cystic fibrosis studies. Lab Anim 2008;42(4):389-412. Review of animal models for CF research.
209. Ostrowski LE, Yin W, Diggs PS, et al. Expression of CFTR from a ciliated cell-specific promoter is ineffective at correcting nasal potential difference in CF mice. Gene Ther 2007;14(20):1492-501 (Pubitemid 47500652)
210. Griesenbach U, Alton EWFW. Cystic fibrosis: Ferreting with fibroblasts for cystic fibrosis. Gene Ther 2009;16(1):1-2
211. Sehgal A, Presente A, Engelhardt JF. Developmental expression patterns of CFTR in ferret tracheal surface airway and submucosal gland epithelia. Am J Respir Cell Mol Biol 1996;15(1):122-31 (Pubitemid 126439863)
212. Sun X, Yan Z, Yi Y, et al. Adeno-associated virus-targeted disruption of the CFTR gene in cloned ferrets. J Clin Invest 2008;118(4):1578-83 (Pubitemid 351500451)
213. Sun X, Sui H, Fisher JT, et al. Disease phenotype of a ferret CFTR-knockout model of cystic fibrosis. J Clin Invest 2010;120(9):3149-60
214. Rogers CS, Hao Y, Rokhlina T, et al. Production of CFTR-null and CFTR-DF508 heterozygous pigs by adeno-associated virus-mediated gene targeting and somatic cell nuclear transfer. J Clin Invest 2008;118(4):1571-7 (Pubitemid 351500450)