Preclinical therapeutic efficacy of the ciprofloxacin‐eluting sinus stent for Pseudomonas aeruginosa sinusitis

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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.

Section: Discussionmentioning

confidence: 99%

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

Cho

Lim

Mackey

et al. 2019

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“…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 . Furthermore, the dual‐coating (hydrophilic [inner = ciprofloxacin] and hydrophobic [outer = ivacaftor] layers) technique had the additional advantage of a sustained controlled release of the 2 drugs.…”

mentioning

confidence: 99%

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

Lim

McCormick

Skinner

et al. 2019

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Background: Pseudomonas aeruginosa is common in chronic rhinosinusitus (CRS) and frequently resistant to antibiotic treatment. We recently described the ciprofloxacin and ivaca or-releasing biodegradable sinus stent (CISS)a drug-delivery system that administers ciprofloxacin and the mucociliary activator (ivaca or) at high local concentrations with prolonged mucosal contact time and sustained delivery. The objective of this study is to evaluate the efficacy of the CISS in a rabbit model of P aeruginosa (PAO1 strain) sinusitis.Methods: Ciprofloxacin/ivaca or (double layer) was coated on biodegradable poly-D/L-lactic acid (PLLA). A total of 10 sinus stents (5 bare PLLA stent controls, 5 CISSs) were placed unilaterally in rabbit maxillary sinuses via dorsal sinusotomy a er inducing infection for 1 week with PAO1. Animals were assessed 3 weeks a er stent insertion with sinus culture, nasal endoscopy, computed tomography scan, histopathology, and in-vivo sinus potential difference (SPD) assay.Results: Rabbits treated with CISS had significant reductions in computed tomography ( Kerschner scale: control, 0.55 ± 0.92; CISS, −5.92 ± 1.69; p = 0.024) and endoscopy (control, 4.0 ± 0.0; CISS, 1.875 ± 0.74; p = 0.003) scores.A 2-log reduction of PAO1 was observed (control, −2.14 ± 0.77; CISS, 1.84 ± 1.52; p = 0.047). SPD revealed significantly increased Cl − transport in the CISS group compared with the control group (Cl − -free + forskolin PD: control, −4.23 ± 1.04 mV; CISS, −18.36 ± 6.31 mV; p = 0.026). Finally, marked improvements were noted in the histology of the mucosa and submucosa in treated animals. Conclusion:The CISS had robust clinical efficacy in treating P aeruginosa rabbit sinusitis. The innovative design of double-layered drug coating on the surface of the biodegradable stent may provide therapeutic advantages over current treatment strategies for P aeruginosa sinusitis. C 2019 ARS-AAOA, LLC. How to Cite this Article:Lim D-J, McCormick J, Skinner D, et al. Controlled delivery of ciprofloxacin and ivaca or via sinus stent in a preclinical model of Pseudomonas sinusitis. Int Forum Allergy Rhinol. 2020;10:481-488.P seudomonas aeruginosa is one of the most common causes of chronic, biofilm-based sinus infection in

“…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.…”

Section: Resultsmentioning

confidence: 98%

“…In addition to safety concerns regarding tendinitis and tendon rupture with systemic administration, ciprofloxacin has known broad‐spectrum activity and is frequently prescribed for CRS patients. Therefore, topical stent delivery could provide effective elimination of multidrug‐resistant organisms while significantly abrogating serious side effects …”

Section: Resultsmentioning

confidence: 99%

Future topical medications in chronic rhinosinusitis

Miyake

Bleier

2019

Background:Research has progressed rapidly in recent decades to be er understand the etiopathogenesis and management paradigms of chronic rhinosinusitis (CRS). Although oral antibiotics o en mitigate symptoms in acute CRS exacerbations, eradication of polymicrobial biofilms and multidrug-resistant bacteria remains a challenge. The goal of this review is to summarize and discuss the potential and pitfalls of topical medications in the treatment of CRS. Methods:A related literature review was performed using PubMed and Scopus, with only the English database included. Results:The main therapies were selected and separated in sections. Details regarding future topical treatments of CRS were summarized and discussed. Conclusion:The ease of access of the sinonasal mucosa positions CRS as a disease with high potential for local topical treatment. The ultimate adoption of topical agents will require continued expansion of our understanding of novel local targets in CRS as well as improved methods to deliver and retain the drug of interest at the site of activity. C 2019 ARS-AAOA, LLC.