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

Abstract

Background:We recently developed a novel ciprofloxacincoated sinus stent capable of releasing antibiotics over a sustained period of time. Ivaca or 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 ivaca or-releasing biodegradable sinus stent (CISS) in vitro. Methods: A CISS was created by coating ciprofloxacin/ivacaor-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 ivaca or-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 a er 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 (RO-DUs 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. C 2019 ARS-AAOA, LLC.

Future topical medications in chronic rhinosinusitis

“…Furthermore, in 2019, Cho et al published an in‐vitro evaluation of ciprofloxacin with an ivacaftor‐coated sinus stent to eradicate P aeruginosa biofilms. They noted a significant reduction in P aeruginosa biofilm formation after a sustained drug release through 21 days, confirming their previous study showing ivacaftor enhancing ciprofloxacin's antimicrobial activity against P aeruginosa …”

“…The group subsequently used the same animal model to evaluate the CSS for treatment of sinonasal P aeruginosa biofilms and demonstrated a robust therapeutic efficacy through the reduction of bacterial load and biofilm formation after 2‐week stent placement . In addition, as described previously in the CFTR modulator section, the association of ciprofloxacin and ivacaftor‐coated sinus stent was analyzed and also demonstrated sustained delivery of drug, leading to a marked reduction in P aeruginosa biofilm formation.…”

“…The expressive clinical benefits reported for oral ivacaftor are unfortunately counterbalanced with its high cost . Nevertheless, Cho et al performed several studies showing the potential of different topical presentations and possible associations of ivacaftor as a solution to combine the benefits of the CFTR modulator with effective lower doses, outweighing the exorbitant costs associated with CF treatment and non‒CF‐related CRS.…”

Controlled delivery of ciprofloxacin and ivacaftor via sinus stent in a preclinical model of Pseudomonas sinusitis

“…In addition, combining 2 or more distinct antibiotics represents a common strategy in treating multidrug‐resistant bacterial infections to broaden the antimicrobial spectrum, generate synergistic effects, and counteract antibiotic resistance . Agents that enhance the antimicrobial activity of currently available antibiotics may also represent a valuable and cost‐effective means for improving clinical efficacy . To improve the characteristics of the CSS, we recently developed a ciprofloxacin and ivacaftor‒coated sinus stent (CISS), which was found to maintain a uniform coating and provide a marked reduction in P aeruginosa biofilm formation in vitro .…”

The impact of Lactococcus lactis (probiotic nasal rinse) co‐culture on growth of patient‐derived strains of Pseudomonas aeruginosa

“…Respiratory infections with P. aeruginosa in CRS populations are particularly detrimental and current therapeutic strategies consist of nasal rinses, corticosteroids, and antibiotics. The pathogenicity of P. aeruginosa includes biofilm formation (decreasing the capability of antibiotic treatment to reach bacteria) and acquired antibiotic resistance, which complicates the strategy for eliminating infections and has encouraged the development of alternate treatment options . Alexandre et al .…”