The effect of particle size of inhaled tobramycin dry powder on the eradication of Pseudomonas aeruginosa biofilms.

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  • Author(s): Aljalamdeh R;Aljalamdeh R; Price R; Price R; Jones MD; Jones MD; Bolhuis A; Bolhuis A
  • Source:
    European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences [Eur J Pharm Sci] 2021 Mar 01; Vol. 158, pp. 105680. Date of Electronic Publication: 2020 Dec 22.
  • Publication Type:
    Journal Article
  • Language:
    English
  • Additional Information
    • Source:
      Publisher: Elsevier Science B.V Country of Publication: Netherlands NLM ID: 9317982 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1879-0720 (Electronic) Linking ISSN: 09280987 NLM ISO Abbreviation: Eur J Pharm Sci Subsets: MEDLINE
    • Publication Information:
      Publication: Amsterdam : Elsevier Science B.V
      Original Publication: Amsterdam ; New York : Elsevier, c1993-
    • Subject Terms:
      Pseudomonas Infections* ; Tobramycin*/therapeutic use; Administration, Inhalation ; Anti-Bacterial Agents/pharmacology ; Anti-Bacterial Agents/therapeutic use ; Biofilms ; Humans ; Particle Size ; Powders ; Pseudomonas aeruginosa
    • Abstract:
      Pseudomonas aeruginosa is the predominant opportunistic bacterium that causes chronic respiratory infections in cystic fibrosis (CF) patients. This bacterium can form biofilms, which are structured communities of cells encased within a self-produced matrix. Such biofilms have a high level of resistance to multiple classes of antibiotics. A widely used treatment of P. aeruginosa lung infections in CF patients is tobramycin dry powder inhalation. The behaviour of particles in the lung has been well studied, and dry powder inhalers are optimised for optimal dispersion of the drug into different zones of the lung. However, one question that has not been addressed is whether the size of an antibiotic particle influences the antibiofilm activity against P. aeruginosa. We investigated this by fractionating tobramycin particles using a Next Generation Impactor (NGI). The fractions obtained were then tested in an in vitro model on P. aeruginosa biofilms. The results indicate that the antibiofilm activity of tobramycin dry powder inhaler can indeed be influenced by the particle size. Against P. aeruginosa biofilms of two clinical isolates, smaller tobramycin particles (aerodynamic diameter <2.82 µm) showed better efficacy by approximately 20% as compared to larger tobramycin particles (aerodynamic diameter <11.7 µm) However, this effect was only observed when biofilms were treated for 3 hours, whereas there was no difference after treatment for 24 hours. This suggests that in our model the rate of dissolution of larger particles limits the effectiveness of tobramycin over a 3-hour time period, which is relevant as this is equivalent to the time in which most tobramycin is cleared from the lung.
      (Copyright © 2020. Published by Elsevier B.V.)
    • Contributed Indexing:
      Keywords: Next Generation Impactor (NGI); Pseudomonas aeruginosa; biofilms; dry powder inhaler; particle size; tobramycin
    • Accession Number:
      0 (Anti-Bacterial Agents)
      0 (Powders)
      VZ8RRZ51VK (Tobramycin)
    • Publication Date:
      Date Created: 20201221 Date Completed: 20210621 Latest Revision: 20210621
    • Publication Date:
      20240829
    • Accession Number:
      10.1016/j.ejps.2020.105680
    • Accession Number:
      33346008