Skip to main content
SpringerLink
Log in

Efficacy of Tobramycin Conjugated to Superparamagnetic Iron Oxide Nanoparticles in Treating Cystic Fibrosis Infections

  • Articles
  • Published:
MRS Online Proceedings Library Aims and scope

Abstract

Cystic fibrosis (CF) is an inherited childhood-onset life-shortening disease. It is characterized by increased respiratory production, leading to airway obstruction, chronic lung infection and inflammatory reactions. The most common bacteria causing persisting infections in people with CF is Pseudomonas aeruginosa. Superparamagnetic Fe3O4 iron oxide nanoparticles (NPs) conjugated to the antibiotic (tobramycin), guided by a gradient of the magnetic field or subjected to an oscillating magnetic field, show promise in improving the drug delivery across the mucus and P. aeruginosa biofilm to the bacteria. The question remains whether tobramycin needs to be released from the NPs after the penetration of the mucus barrier in order to act upon the pathogenic bacteria. We used a zero-length 1-ethyl-3-[3-dimethylaminopropyl] carbodiimide hydrochloride (EDC) crosslinking agent to couple tobramycin, via its amine groups, to the carboxyl groups on Fe3O4 NPs capped with citric acid. The therapeutic efficiency of Fe3O4 NPs attached to the drug versus that of the free drug was investigated in P. aeruginosa culture.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. R. L. Gibson, J. L. Burns, and B. W. Ramsey, “Pathophysiology and management of pulmonary infections in cystic fibrosis”, Am. J. Respir. Crit. Care Med. 168, 918–951, 2003.

    Article  Google Scholar 

  2. Cystic Fibrosis Foundation, www.cff.org, accessed on July 20, 2013.

  3. M. J. Welsh, B. W. Ramsey, F. Accurso, and G. Cutting, “Cystic Fibrosis”, in The Metabolic and Molecular Basis of Inherited Diseases (C. R. Scriver, A. L. Beaudet, W. S. Sly, and D. Valle, Eds.), 8th Ed., McGraw-Hill, New York 2001, pp. 5121–5188.

  4. M. Mense, P. Vergani, D. M. White, G. Altberg, A. C. Nairn, and D. C.Gadsby, “In vivo phosphorylation of CFTR promotes formation of a nucleotide-binding domain heterodimer”, The EMBO J. 25, 4728 – 4739, 2006.

  5. M. E. Hodson and D. M. Geddes, Cystic Fibrosis, Chapman and Hall Medical, London 1995.

    Google Scholar 

  6. J. L. Burns, B. W. Ramsey, and A. L. Smith, “Clinical manifestations and treatment of pulmonary infections in cystic fibrosis”, Adv. Pediatr. Infect. Dis. 8, 53–66, 1993.

    CAS  Google Scholar 

  7. N. Hoiby, “Antibiotic therapy for chronic infection of Pseudomonas in the lung”, Annu. Rev. Med. 44, 1–10, 1993.

    Article  CAS  Google Scholar 

  8. L. Garcia-Contreras and A. J. Hickey, “Aerosol treatment for cystic fibrosis”, Crit. Rev. Ther. Drug Carr. Syst. 20, 317–356, 2003.

    Article  CAS  Google Scholar 

  9. J. A. Voynow and B. K. Rubin, “Mucins, mucus, and sputum”, Chest 135 (2), 505–512, Feb. 2009.

    Article  CAS  Google Scholar 

  10. B. K. Rubin, “Mucus structure and properties in cystic fibrosis”, Paediatric Resp. Rev. 8 (1), 4–7, March 2007.

    Article  Google Scholar 

  11. H. Matsui, B. R. Grubb, R. Tarran, S. H. Randell, J. T. Gatzy, C. W. Davis, and R. C. Boucher, “Evidence for periciliary liquid layer depletion, not abnormal ion composition, in the pathogenesis of cystic fibrosis airway disease”, Cell 95 (7), 1005–1015, 1998.

    Article  CAS  Google Scholar 

  12. R. C. Boucher, “New concepts of the pathogenesis of cystic fibrosis lung disease”, Eur. Respir. J. 23, 146–158, 2004.

    Article  CAS  Google Scholar 

  13. J. Perez-Vilar and R. C. Boucher, “Reevaluating gel-forming mucins’ roles in cystic fibrosis lung disease” Free Rad. Bio. Med. 37, 1564–1577, 2004.

    Article  CAS  Google Scholar 

  14. J. Emerson, M. Rosenfeld, S. McNamara, B. Ramsey, and R. L. Gibson, “Pseudomonas aeruginosa and other predictors of mortality and morbidity in young children with cystic fibrosis”, Pediatr. Pulmonol. 34, 91–100, 2002.

    Article  Google Scholar 

  15. M. Fegan, P. Francis, A. C. Hayward, G. H. Davis, and J. A. Fuerst, “Phenotypic conversion of Pseudomonas aeruginosa in cystic fibrosis”, J. Clin. Microbiol. 28, 1143–1146, 1990.

    Article  CAS  Google Scholar 

  16. J. W. Costerton, P. S. Stewart, and E. P. Greenberg, “Bacterial biofilms: A common cause of persistent infections”, Science 284, 1318–1322, 1999.

    Article  CAS  Google Scholar 

  17. P. K. Singh, A. L Schaefer, M. R. Parsek, T. O. Moninger, M. J. Welsh, and E. P. Greenberg, “Quorum-sensing signals indicate that cystic fibrosis lungs are infected with bacterial biofilms”, Nature 407, 762–764, 2000.

    Article  CAS  Google Scholar 

  18. D. A. Cabral, B. A. Loh, and D. P. Speert, “Mucoid Pseudomonas aeruginosa resists nonopsonic phagocytosis by human neutrophils and macrophages”, Pediatr. Res. 22, 429–431, 1987.

    Article  CAS  Google Scholar 

  19. G. B. Pier, F. Coleman, M. Grout, M. Franklin, and D. E. Ohman, “Role of alginate O acetylation in resistance of mucoid Pseudomonas aeruginosa to opsonic phagocytosis”, Infect. Immun. 69, 1895–1901, 2001.

    Article  CAS  Google Scholar 

  20. H. Anwar, M. Dasgupta, K. Lam, and J. W. Costerton, “Tobramycin resistance of mucoid Pseudomonas aeruginosa biofilm grown under iron limitation”, J. Antimicrob. Chemother. 24, 647–655, 1989.

    Article  CAS  Google Scholar 

  21. N. A. Hodges and C. A. Gordon, “Protection of Pseudomonas aeruginosa against ciprofloxacin and β-lactams by homologous alginate”, Antimicrob. Agents Chemother. 35, 2450–2452, 1991.

    Article  CAS  Google Scholar 

  22. M. Whiteley, M. G. Bangera, R. E. Bumgarner, M. R. Parsek, G. M. Teitzel, S. Lory, and E. P. Greenberg, “Gene expression in Pseudomonas aeruginosa biofilms”, Nature 413 (6858) 860–864, 25 Oct. 2001.

    Article  CAS  Google Scholar 

  23. R. M. Harshey, “Bacterial motility on a surface: Many ways to a common goal”, Annu. Rev. Microbiol. 57, 249–273, 2003.

    Article  CAS  Google Scholar 

  24. H. P Schweizer, “Efflux as a mechanism of resistance to antimicrobials in Pseudomonas aeruginosa and related bacteria: Unanswered questions”, Genet. Mol. Res. 2, 48–62, 2003.

    Google Scholar 

  25. F. Ratjen, G. Döring, and W. H. Nikolaizik, “Effect of inhaled tobramycin on early Pseudomonas aeruginosa colonisation in patients with cystic fibrosis”, Lancet 358, 983–984, 2001.

    Article  CAS  Google Scholar 

  26. M. Griese, I. Müller, and D. Reinhardt, “Eradication of initial Pseudomonas aeruginosa colonization in patients with cystic fibrosis”, Eur. J. Med. Res. 7 (2), 79–80, 21 Feb. 2002.

    Google Scholar 

  27. R. R. Qiao, C. H. Yang, and M. Y. Gao, “Superparamagnetic iron oxide nanoparticles: From preparations to in vivo MRI applications”, J. Mater. Chem. 19, 6274–6293, 2009.

    Article  CAS  Google Scholar 

  28. R. T. Castaneda, A. Khurana, R. Khan, and H. E. Daldrup-Link, “Labeling stem cells with ferumoxytol, an FDA-approved iron oxide nanoparticle”, J. Vis. Exp. 57, Art. e3482, 4 Nov. 2011.

    Google Scholar 

  29. Y. Sahoo, A. Goodarzi, M. T. Swihart, T. Y. Ohulchanskyy, N. Kaur, E. P. Furlani, and P. N. Prasad, “Aqueous ferrofluid of magnetite nanoparticles: Fluorescence labeling and magnetophoretic control”, J. Phys. Chem. B 109, 3879–3885, 2005.

    Article  CAS  Google Scholar 

  30. H. Iida, K. Takayanagi, T. Nakanishi, and T. Osaka, “Synthesis of Fe3O4 nanoparticles with various sizes and magnetic properties by controlled hydrolysis”, J. Colloid. Interface Sci. 314, 274–280, 2007.

    Article  CAS  Google Scholar 

  31. L. M. Armijo, Y. I. Brandt, N. J. Withers, J. B. Plumley, N. C. Cook, A. C. Rivera, S. Yadav, G. A. Smolyakov, T. Monson, D. L. Huber, H. D. C. Smyth, and M. Osiński, “Multifunctional superparamagnetic nanocrystals for imaging and targeted drug delivery to the lung”, Colloidal Nanocrystals for Biomedical Applications VII (W. J. Parak, M. Osiński, and K. Yamamoto, Eds.), SPIE International Symp. on Biomedical Optics BiOS 2012, San Francisco, CA, 21–23 Jan. 2012, Proc. SPIE 8232, Paper 82320M (11 pp.).

  32. D. J. Herman, P. Ferguson, S. Cheong, I. F. Hermans, B. J. Ruck, K. M. Allan, S. Prabakar, J. L. Spencer, C. D. Lendrum, and R. D. Tilley, “Hot-injection synthesis of iron/iron oxide core/shell nanoparticles for T2 contrast enhancement in magnetic resonance imaging”, Electr. Suppl. Material (ESI), Chem. Communic. 47, 9221–9223, 2011.

    CAS  Google Scholar 

  33. G. T. Hermanson, Bioconjugate Techniques, 2nd Ed, Academic Press 2008, p. 598.

  34. S. Shakil, R. Khan, R. Zarrilli, and A. U. Khan, “Aminoglycosides versus bacteria - A description of the action, resistance mechanism, and nosocomial battleground”, J. Biomed. Sci. 15 (1), 5–14, Jan. 2008.

    Article  CAS  Google Scholar 

  35. L. Saiman, “Microbiology of early CF lung disease”, Paediatr. Respir. Rev. 5 (Suppl A), S367–S369, 2004.

    Article  Google Scholar 

  36. F. Le Goffic, M. L. Capmau, F. Tangy, and M. Baillarge, “Mechanism of action of aminoglycoside antibiotics. Binding studies of tobramycin and its 6’-n-acetyl derivative to the bacterial ribosome and its subunits”, Eur. J. Biochem. 102, 73–81, 1979.

    Article  CAS  Google Scholar 

  37. H. Nikaido and R. E. W. Hancock, “Outer membrane permeability of Pseudomonas aeruginosa”, in The Bacteria: A Treatise on Structure and Function (J. R. Sokatch, Ed.), Academic Press, London 1986, pp. 145–193.

  38. H. Nikaido, “Nonspecific and specific permeation channels of the Pseudomonas aeruginosa outer membrane”, in Pseudomonas. Molecular Biology and Biotechnology (E. Galli, S. Silver, and B. Witholt, Eds.), Am. Soc. Microbiol., Washington, DC 1992, pp. 146–154.

  39. R. Y. Stanier, N. J. Palleroni, and M. Doudoroff, “The aerobic pseudomonads: A taxonomic study”, J. Gen. Microbiol. 43 (2), 159–271, May 1966.

    Article  CAS  Google Scholar 

  40. J. B.Morrow, C. P. Arango, and R. D. Holbrook, “Association of quantum dot nanoparticles with Pseudomonas aeruginosa biofilm”, J. Environ. Qual. 39, 1934–1941, 2010.

    Article  CAS  Google Scholar 

  41. J. McQuillan, Bacterial-Nanoparticle Interactions, Ph.D. Dissertation, Univ. of Exeter, UK, 2010.

Download references

Author information

Authors and Affiliations

  1. Center for High Technology Materials, University of New Mexico, 1313 Goddard SE, Albuquerque, 87106-4343, NM, USA

    Marek Osiński, Yekaterina I. Brandt, Leisha M. Armijo, Michael Kopciuch, Nathan. J. Withers, Nathaniel C. Cook & Gennady A. Smolyakov

  2. Department of Biochemistry and Molecular Biology, School of Medicine, University of New Mexico, Albuquerque, 87131, NM, USA

    Natalie L. Adolphi

  3. College of Pharmacy, University of Texas at Austin, Austin, 78712, TX, USA

    Hugh D. C. Smyth

Authors
  1. Marek Osiński
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yekaterina I. Brandt
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Leisha M. Armijo
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Michael Kopciuch
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Nathan. J. Withers
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Nathaniel C. Cook
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Natalie L. Adolphi
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Gennady A. Smolyakov
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Hugh D. C. Smyth
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Osiński, M., Brandt, Y.I., Armijo, L.M. et al. Efficacy of Tobramycin Conjugated to Superparamagnetic Iron Oxide Nanoparticles in Treating Cystic Fibrosis Infections. MRS Online Proceedings Library 1617, 127–137 (2013). https://doi.org/10.1557/opl.2013.1175

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1557/opl.2013.1175

Search

Navigation