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

• Published in: International forum of allergy & rhinology 2019-05, Vol.9 (5), p.486-492
• Main Authors: Cho, Do‐Yeon, Lim, Dong‐Jin, Mackey, Calvin, Weeks, Christopher G., Garcia, Jaime A. Peña, Skinner, Daniel, Zhang, Shaoyan, McCormick, Justin, Woodworth, Bradford A.
• Format: Article
• Language: English
• Subjects: Aminophenols - administration & dosage; Aminophenols - chemistry; Ammonium; Anti-Bacterial Agents - administration & dosage; Anti-Bacterial Agents - chemistry; Antibiotics; Bactericidal activity; Biodegradability; Biofilms; Biofilms - drug effects; Chloride Channel Agonists - administration & dosage; Chloride Channel Agonists - chemistry; chronic rhinosinusitis; Ciprofloxacin; Ciprofloxacin - administration & dosage; Ciprofloxacin - chemistry; Coatings; Conductance; Cystic fibrosis; Drug delivery; Drug Liberation; Drug-Eluting Stents; Implants; ivacaftor; Nanoparticles; Nanoparticles - administration & dosage; Nanoparticles - chemistry; Optical density; Polylactic Acid-Polyglycolic Acid Copolymer - administration & dosage; Polylactic Acid-Polyglycolic Acid Copolymer - chemistry; Pseudomonas aeruginosa; Pseudomonas aeruginosa - drug effects; Pseudomonas aeruginosa - physiology; Pseudomonas Infections; Quinolones - administration & dosage; Quinolones - chemistry; recalcitrant sinusitis; Rhinitis; Scanning electron microscopy; sinus stent biofilm; Sinuses; Sinusitis; Zeta potential
• ISSN: 2042-6976; 2042-6984; 2042-6984
• DOI: 10.1002/alr.22285

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.