In-vitro evaluation of a ciprofloxacin- and ivacaftor-coated sinus stent against Pseudomonas aeruginosa biofilms

Int Forum Allergy Rhinol. 2019 May;9(5):486-492. doi: 10.1002/alr.22285. Epub 2019 Jan 31.

Abstract

Background: We recently developed a novel ciprofloxacin-coated sinus stent capable of releasing antibiotics over a sustained period of time. Ivacaftor is a cystic fibrosis transmembrane conductance regulator (CFTR) potentiator that has synergistic bactericidal activity with ciprofloxacin and also enhances sinus mucociliary clearance. The objective of this study was to optimize and evaluate the efficacy of a ciprofloxacin- and ivacaftor-releasing biodegradable sinus stent (CISS) in vitro.

Methods: A CISS was created by coating ciprofloxacin/ivacaftor-embedded nanoparticles with an acrylate and ammonium methacrylate copolymer onto a biodegradable poly-L-lactic acid stent. In-vitro evaluation of the CISS included: (1) assessment of drug stability in nanoparticles by zeta potential, and drug-coating stability within the CISS using scanning electron microscopy (SEM); (2) determination of ciprofloxacin- and ivacaftor-release kinetics; and (3) assessment of anti-Pseudomonas aeruginosa biofilm formation by calculating relative optical density units (RODUs) compared with control stents at 590-nm optical density.

Results: The presence of drugs and a uniform coating on the stent were confirmed by zeta potential and SEM. Sustained drug release was observed through 21 days without an initial burst release. Anti-biofilm formation was observed after placing the CISS for 3 days onto a preformed 1-day P aeruginosa biofilm. The CISS significantly reduced biofilm mass compared with bare stents and controls (RODUs at 590-nm optical density; CISS, 0.31 ± 0.01; bare stent, 0.78 ± 0.12; control, 1.0 ± 0.00; p = 0.001; n = 3).

Conclusion: The CISS maintains a uniform coating and sustained delivery of drugs providing a marked reduction in P aeruginosa biofilm formation. Further studies evaluating the efficacy of CISS in a preclinical model are planned.

Keywords: Pseudomonas aeruginosa; chronic rhinosinusitis; ciprofloxacin; ivacaftor; recalcitrant sinusitis; sinus stent biofilm.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aminophenols / administration & dosage*
  • Aminophenols / chemistry
  • Anti-Bacterial Agents / administration & dosage*
  • Anti-Bacterial Agents / chemistry
  • Biofilms / drug effects
  • Chloride Channel Agonists / administration & dosage*
  • Chloride Channel Agonists / chemistry
  • Ciprofloxacin / administration & dosage*
  • Ciprofloxacin / chemistry
  • Drug Liberation
  • Drug-Eluting Stents
  • Nanoparticles / administration & dosage
  • Nanoparticles / chemistry
  • Polylactic Acid-Polyglycolic Acid Copolymer / administration & dosage
  • Polylactic Acid-Polyglycolic Acid Copolymer / chemistry
  • Pseudomonas Infections
  • Pseudomonas aeruginosa / drug effects
  • Pseudomonas aeruginosa / physiology
  • Quinolones / administration & dosage*
  • Quinolones / chemistry

Substances

  • Aminophenols
  • Anti-Bacterial Agents
  • Chloride Channel Agonists
  • Quinolones
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • ivacaftor
  • Ciprofloxacin