Nanomedicine: Nanotechnology, Biology and Medicine
Volume 6, Issue 2 , Pages 237-244 , April 2010

Nanodelivery in airway diseases: Challenges and therapeutic applications

  • Indrajit Roy, MS, PhD

      Affiliations

    • Institute for Lasers, Photonics and Biophotonics, Department of Chemistry, State University of New York, Buffalo, New York, USA
  • ,
  • Neeraj Vij, MS, PhD

      Affiliations

    • Department of Pediatric Respiratory Sciences and Institute of NanoBioTechnology, Johns Hopkins School of Medicine, Baltimore, Maryland, USA
    • Corresponding Author InformationCorresponding author: Baltimore, MD 21287, USA.

Received 23 March 2009 ,Accepted 4 July 2009.

References 

  1. Hussain AA. Intranasal drug delivery. Adv Drug Del Rev. 1998;29:39–49
  2. Merkus FWHM, Schipper NGM, Hermens WAJJ, Romeijn SC, Verhoef JC. Absorption enhancers in nasal drug delivery: efficacy and safety. J Controlled Release. 1993;24:201–208
  3. Sanders N, Rudolph C, Braeckmans K, De Smedt SC, Demeester J. Extracellular barriers in respiratory gene therapy. Adv Drug Deliv Rev. 2009;61:115–127
  4. Rytting E, Nguyen J, Wang X, Kissel T. Biodegradable polymeric nanocarriers for pulmonary drug delivery. Expert Opin Drug Deliv. 2008;5:629–639
  5. Card JW, Zeldin DC, Bonner JC, Nestmann ER. Pulmonary applications and toxicity of engineered nanoparticles. Am J Physiol Lung Cell Mol Physiol. 2008;295:L400–L411
  6. Yang W, Peters JI, Williams RO. Inhaled nanoparticles—a current review. Int J Pharm. 2008;356:239–247
  7. Griesenbach U, Geddes DM, Alton EW. Advances in cystic fibrosis gene therapy. Curr Opin Pulm Med. 2004;10:542–546
  8. Mueller C, Flotte TR. Gene therapy for cystic fibrosis. Clin Rev Allergy Immunol. 2008;35:164–178
  9. Wang JT, Peng DY, Chen M, Ye JS. Gene delivery for lung cancer using nonviral gene vectors. Pharmazie. 2007;62:723–726
  10. Suzuki M, Matsuse T, Isigatsubo Y. Gene therapy for lung diseases: development in the vector biology and novel concepts for gene therapy applications. Curr Mol Med. 2001;1:67–79
  11. Azarmi S, Roa WH, Lobenberg R. Targeted delivery of nanoparticles for the treatment of lung diseases. Adv Drug Deliv Rev. 2008;60:863–875
  12. Rosenecker J, Huth S, Rudolph C. Gene therapy for cystic fibrosis lung disease: current status and future perspectives. Curr Opin Mol Ther. 2006;8:439–445
  13. Boussif O, Lezoualc'h F, Zanta MA. A versatile vector for gene and oligonucleotide transfer into cells in culture and in vivo: polyethylenimine. Proc Natl Acad Sci U S A. 1995;92:7297–7301
  14. Felgner PL, Gadek TR, Holm M. Lipofection: a highly efficient, lipid-mediated DNA-transfection procedure. Proc Natl Acad Sci U S A. 1987;84:7413–7417
  15. Roy I, Mitra S, Maitra A, Mozumdar S. Calcium phosphate nanoparticles as novel non-viral vectors for targeted gene delivery. Int J Pharm. 2003;250:25–33
  16. Roy I, Ohulchanskyy TY, Bharali DJ. Optical tracking of organically modified silica nanoparticles as DNA carriers: a nonviral, nanomedicine approach for gene delivery. Proc Natl Acad Sci U S A. 2005;102:279–284
  17. Lopez-Vidriero MT, Reid L. Bronchial mucus in health and disease. Br Med Bull. 1978;34:63–74
  18. Deneuville E, Perrot-Minot C, Pennaforte F. Revisited physicochemical and transport properties of respiratory mucus in genotyped cystic fibrosis patients. Am J Respir Crit Care Med. 1997;156:166–172
  19. King M. The role of mucus viscoelasticity in cough clearance. Biorheology. 1987;24:589–597
  20. Lai SK, Wang YY, Hanes J. Mucus-penetrating nanoparticles for drug and gene delivery to mucosal tissues. Adv Drug Deliv Rev. 2009;61:158–171
  21. Gersting SW, Schillinger U, Lausier J. Gene delivery to respiratory epithelial cells by magnetofection. J Gene Med. 2004;6:913–922
  22. Colina AR, Aumont F, Deslauriers N, Belhumeur P, de Repentigny L. Evidence for degradation of gastrointestinal mucin by Candida albicans secretory aspartyl proteinase. Infect Immun. 1996;64:4514–4519
  23. Connaris S, Greenwell P. Glycosidases in mucin-dwelling protozoans. Glycoconj J. 1997;14:879–882
  24. Alpar HO, Somavarapu S, Atuah KN, Bramwell VW. Biodegradable mucoadhesive particulates for nasal and pulmonary antigen and DNA delivery. Adv Drug Deliv Rev. 2005;57:411–430
  25. Mohapatra SS. Mucosal gene expression vaccine: a novel vaccine strategy for respiratory syncytial virus. Pediatr Infect Dis J. 2003;22(2 Suppl):S100–S103[discussion S103-104]
  26. Davis SS. Biomedical applications of nanotechnology-implications for drug targeting and gene therapy. Trends Biotechnol. 1997;15:217–224
  27. Allen TM. Long-circulating (sterically stabilized) liposomes for targeted drug delivery. Trends Pharmacol Sci. 1994;15:215–220
  28. Ogris M, Brunner S, Schuller S, Kircheis R, Wagner E. PEGylated DNA/transferrin-PEI complexes: reduced interaction with blood components, extended circulation in blood and potential for systemic gene delivery. Gene Ther. 1999;6:595–605
  29. Gopalan B, Ito I, Branch CD, Stephens C, Roth JA, Ramesh R. Nanoparticle based systemic gene therapy for lung cancer: molecular mechanisms and strategies to suppress nanoparticle-mediated inflammatory response. Technol Cancer Res Treat. 2004;3:647–657
  30. Maeda H, Wu J, Sawa T, Matsumura Y, Hori K. Tumor vascular permeability and the EPR effect in macromolecular therapeutics: a review. J Controlled Release. 2000;65:271–284
  31. Foster BJ, Kern JA. HER2-targeted gene transfer. Hum Gene Ther. 1997;8:719–727
  32. Lee RJ, Huang L. Folate-targeted, anionic liposome-entrapped polylysine-condensed DNA for tumor cell-specific gene transfer. J Biol Chem. 1996;271:8481–8487
  33. Sosnowski BA, Gonzalez AM, Chandler LA, Buechler YJ, Pierce GF, Baird A. Targeting DNA to cells with basic fibroblast growth factor (FGF2). J Biol Chem. 1996;271:33647–33653
  34. Hood JD, Bednarski M, Frausto R. Tumor regression by targeted gene delivery to the neovasculature. Science. 2002;296:2404–2407
  35. Ross GF, Morris RE, Ciraolo G. Surfactant protein A-polylysine conjugates for delivery of DNA to airway cells in culture. Hum Gene Ther. 1995;6:31–40
  36. Wiewrodt R, Thomas AP, Cipelletti L, Christofidou-Solomidou M, Weitz DA, Feinstein SI, et al. Size-dependent intracellular immunotargeting of therapeutic cargoes into endothelial cells. Blood. 2002;99:912–922
  37. Fajac I, Briand P, Monsigny M, Midoux P. Sugar-mediated uptake of glycosylated polylysines and gene transfer into normal and cystic fibrosis airway epithelial cells. Human Gene Ther. 1999;10:395–406
  38. Hillaireau H, Couvreur P. Nanocarriers' entry into the cell: relevance to drug delivery. Cell Mol Life Sci. 2009;66:2873–2896
  39. Mounkes LC, Zhong W, Cipres-Palacin G, Heath TD, Debs RJ. Proteoglycans mediate cationic liposome-DNA complex-based gene delivery in vitro and in vivo. J Biol Chem. 1998;273:26164–26170
  40. Haensler J, Szoka FC. Polyamidoamine cascade polymers mediate efficient transfection of cells in culture. Bioconjug Chem. 1993;4:372–379
  41. Sonawane ND, Szoka FC, Verkman AS. Chloride accumulation and swelling in endosomes enhances DNA transfer by polyamine-DNA polyplexes. J Biol Chem. 2003;278:44826–44831
  42. Mok KW, Cullis PR. Structural and fusogenic properties of cationic liposomes in the presence of plasmid DNA. Biophys J. 1997;73:2534–2545
  43. Nishikawa M, Huang L. Nonviral vectors in the new millennium: delivery barriers in gene transfer. Hum Gene Ther. 2001;12:861–870
  44. Panyam J, Zhou WZ, Prabha S, Sahoo SK, Labhasetwar V. Rapid endo-lysosomal escape of poly(DL-lactide-co-glycolide) nanoparticles: implications for drug and gene delivery. FASEB J. 2002;16:1217–1226
  45. Curiel DT. High-efficiency gene transfer employing adenovirus-polylysine-DNA complexes. Nat Immun. 1994;13:141–164
  46. Ragnarsson EG, Schoultz I, Gullberg E. Yersinia pseudotuberculosis induces transcytosis of nanoparticles across human intestinal villus epithelium via invasin-dependent macropinocytosis. Lab Invest. 2008;88:1215–1226
  47. Brunner S, Sauer T, Carotta S, Cotten M, Saltik M, Wagner E. Cell cycle dependence of gene transfer by lipoplex, polyplex and recombinant adenovirus. Gene Ther. 2000;7:401–407
  48. Stoffler D, Fahrenkrog B, Aebi U. The nuclear pore complex: from molecular architecture to functional dynamics. Curr Opin Cell Biol. 1999;11:391–401
  49. Rolland A. Nuclear gene delivery: the Trojan horse approach. Expert Opin Drug Deliv. 2006;3:1–10
  50. Zanta MA, Belguise-Valladier P, Behr JP. Gene delivery: a single nuclear localization signal peptide is sufficient to carry DNA to the cell nucleus. Proc Natl Acad Sci U S A. 1999;96:91–96
  51. Subramanian A, Ranganathan P, Diamond SL. Nuclear targeting peptide scaffolds for lipofection of nondividing mammalian cells. Nat Biotechnol. 1999;17:873–877
  52. Bestor TH. Transposons reanimated in mice. Cell. 2005;122:322–325
  53. Mikkelsen JG, Yant SR, Meuse L, Huang Z, Xu H, Kay MA. Helper-independent sleeping beauty transposon-transposase vectors for efficient nonviral gene delivery and persistent gene expression in vivo. Mol Ther. 2003;8:654–665
  54. Yant SR, Meuse L, Chiu W, Ivics Z, Izsvak Z, Kay MA. Somatic integration and long-term transgene expression in normal and haemophilic mice using a DNA transposon system. Nat Genet. 2000;25:35–41
  55. Dupuy AJ, Akagi K, Largaespada DA, Copeland NG, Jenkins NA. Mammalian mutagenesis using a highly mobile somatic sleeping beauty transposon system. Nature. 2005;436:221–226
  56. Rowe SM, Miller S, Sorscher EJ. Cystic fibrosis. N Engl J Med. 2005;352:1992–2001
  57. Wine JJ. The genesis of cystic fibrosis lung disease. J Clin Invest. 1999;103:309–312
  58. Ward CL, Omura S, Kopito RR. Degradation of CFTR by the ubiquitin-proteasome pathway. Cell. 1995;83:121–127
  59. Lee TW, Matthews DA, Blair GE. Novel molecular approaches to cystic fibrosis gene therapy. Biochem J. 2005;387:1–15
  60. Dorin JR, Farley R, Webb S. A demonstration using mouse models that successful gene therapy for cystic fibrosis requires only partial gene correction. Gene Ther. 1996;3:797–801
  61. Zabner J, Cheng SH, Meeker D. Comparison of DNA-lipid complexes and DNA alone for gene transfer to cystic fibrosis airway epithelia in vivo. J Clin Invest. 1997;100:1529–1537
  62. Alton EW, Stern M, Farley R. Cationic lipid-mediated CFTR gene transfer to the lungs and nose of patients with cystic fibrosis: a double-blind placebo-controlled trial. Lancet. 1999;353:947–954
  63. Konstan MW, Davis PB, Wagener JS. Compacted DNA nanoparticles administered to the nasal mucosa of cystic fibrosis subjects are safe and demonstrate partial to complete cystic fibrosis transmembrane regulator reconstitution. Hum Gene Ther. 2004;15:1255–1269
  64. Ziady AG, Gedeon CR, Miller T. Transfection of airway epithelium by stable PEGylated poly-L-lysine DNA nanoparticles in vivo. Mol Ther. 2003;8:936–947
  65. Vij N, Fang S, Zeitlin PL. Selective inhibition of endoplasmic reticulum-associated degradation rescues {Delta}F508-cystic fibrosis transmembrane regulator and suppresses interleukin-8 levels: therapeutic implications. J Biol Chem. 2006;281:17369–17378
  66. Mitchell BS. The proteasome—an emerging therapeutic target in cancer. N Engl J Med. 2003;348:2597–2598
  67. Bross PF, Kane R, Farrell AT. Approval summary for bortezomib for injection in the treatment of multiple myeloma. Clin Cancer Res. 2004;10:3954–3964
  68. Kane RC, Bross PF, Farrell AT, Pazdur R. Velcade: U.S. FDA approval for the treatment of multiple myeloma progressing on prior therapy. Oncologist. 2003;8:508–513
  69. Zhang LN, Karp P, Gerard CJ. Dual therapeutic utility of proteasome modulating agents for pharmaco-gene therapy of the cystic fibrosis airway. Mol Ther. 2004;10:990–1002
  70. Pedemonte N, Lukacs GL, Du K. Small-molecule correctors of defective DeltaF508-CFTR cellular processing identified by high-throughput screening. J Clin Invest. 2005;115:2564–2571
  71. Varga K, Goldstein RF, Jurkuvenaite A. Enhanced cell-surface stability of rescued DeltaF508 cystic fibrosis transmembrane conductance regulator (CFTR) by pharmacological chaperones. Biochem J. 2008;410:555–564
  72. Vij N. AAA ATPase p97/VCP: cellular functions, disease and therapeutic potential. J Cell Mol Med. 2008;
  73. Vij N, Mazur S, Zeitlin PL. CFTR is a negative regulator of NFkappaB mediated innate immune response. PLoS ONE. 2009;4:e4664
  74. Wang Y, Loo TW, Bartlett MC, Clarke DM. Correctors promote maturation of cystic fibrosis transmembrane conductance regulator (CFTR)-processing mutants by binding to the protein. J Biol Chem. 2007;282:33247–33251
  75. Wang Y, Loo TW, Bartlett MC, Clarke DM. Additive effect of multiple pharmacological chaperones on maturation of CFTR processing mutants. Biochem J. 2007;406:257–263
  76. Perlmutter DH. Liver injury in alpha 1-antitrypsin deficiency. Clin Liver Dis. 2000;4:387–408
  77. Brigham KL, Lane KB, Meyrick B. Transfection of nasal mucosa with a normal alpha1-antitrypsin gene in alpha1-antitrypsin-deficient subjects: comparison with protein therapy. Hum Gene Ther. 2000;11:1023–1032
  78. Thomas M, Lu JJ, Chen J, Klibanov AM. Non-viral siRNA delivery to the lung. Adv Drug Deliv Rev. 2007;59:124–133
  79. Akinc A, Zumbuehl A, Goldberg M. A combinatorial library of lipid-like materials for delivery of RNAi therapeutics. Nat Biotechnol. 2008;26:561–569
  80. Moschos SA, Jones SW, Perry MM. Lung delivery studies using siRNA conjugated to TAT(48-60) and penetratin reveal peptide induced reduction in gene expression and induction of innate immunity. Bioconjug Chem. 2007;18:1450–1459
  81. Zhang W, Yang H, Kong X, et al. Inhibition of respiratory syncytial virus infection with intranasal siRNA nanoparticles targeting the viral NS1 gene. Nat Med. 2005;11:56–62

 The authors are supported by grants R025-CR07 and VIJ07IO from the Cystic Fibrosis Foundation and by National Institutes of Health grants CTSA UL RR 025005 and RHL096931 (N.V.). The funders had no role in the decision to publish or in preparation of the manuscript.

PII: S1549-9634(09)00114-2

doi: 10.1016/j.nano.2009.07.001

Nanomedicine: Nanotechnology, Biology and Medicine
Volume 6, Issue 2 , Pages 237-244 , April 2010