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

Publisher: Published for ARS-AAOA by Wiley-Blackwell Country of Publication: United States NLM ID: 101550261 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2042-6984 (Electronic) Linking ISSN: 20426976 NLM ISO Abbreviation: Int Forum Allergy Rhinol Subsets: MEDLINE

Original Publication: Hoboken : Published for ARS-AAOA by Wiley-Blackwell

Aminophenols/*administration & dosage ; Anti-Bacterial Agents/*administration & dosage ; Chloride Channel Agonists/*administration & dosage ; Ciprofloxacin/*administration & dosage ; Quinolones/*administration & dosage; Aminophenols/chemistry ; Anti-Bacterial Agents/chemistry ; Biofilms/drug effects ; Chloride Channel Agonists/chemistry ; 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/chemistry

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.
(© 2019 ARS-AAOA, LLC.)

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P30 DK072482 United States DK NIDDK NIH HHS; R01 HL133006 United States HL NHLBI NIH HHS

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

0 (Aminophenols)
0 (Anti-Bacterial Agents)
0 (Chloride Channel Agonists)
0 (Quinolones)
1SIA8062RS (Polylactic Acid-Polyglycolic Acid Copolymer)
1Y740ILL1Z (ivacaftor)
5E8K9I0O4U (Ciprofloxacin)

Date Created: 20190201 Date Completed: 20200303 Latest Revision: 20240716

20240716

PMC6491263

10.1002/alr.22285

30702211