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We recently described the ciprofloxacin and ivacaftor\u2012releasing biodegradable sinus stent (CISS)\u2015a drug\u2010delivery system that administers ciprofloxacin and the mucociliary activator (ivacaftor) 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 <jats:italic>P aeruginosa<\/jats:italic> (PAO1 strain) sinusitis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Ciprofloxacin\/ivacaftor (double layer) was coated on biodegradable poly\u2010D\/L\u2010lactic 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 after inducing infection for 1 week with PAO1. Animals were assessed 3 weeks after stent insertion with sinus culture, nasal endoscopy, computed tomography scan, histopathology, and in\u2010vivo sinus potential difference (SPD) assay.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Rabbits treated with CISS had significant reductions in computed tomography (\u2206 Kerschner scale: control, 0.55 \u00b1 0.92; CISS, \u22125.92 \u00b1 1.69; <jats:italic>p<\/jats:italic> = 0.024) and endoscopy (control, 4.0 \u00b1 0.0; CISS, 1.875 \u00b1 0.74; <jats:italic>p<\/jats:italic> = 0.003) scores. A 2\u2010log reduction of PAO1 was observed (control, \u22122.14 \u00b1 0.77; CISS, 1.84 \u00b1 1.52; <jats:italic>p<\/jats:italic> = 0.047). SPD revealed significantly increased Cl<jats:sup>\u2212<\/jats:sup> transport in the CISS group compared with the control group (Cl<jats:sup>\u2212<\/jats:sup>\u2010free + forskolin \u0394PD: control, \u22124.23 \u00b1 1.04 mV; CISS, \u221218.36 \u00b1 6.31 mV; <jats:italic>p<\/jats:italic> = 0.026). Finally, marked improvements were noted in the histology of the mucosa and submucosa in treated animals.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The CISS had robust clinical efficacy in treating <jats:italic>P aeruginosa<\/jats:italic> rabbit sinusitis. The innovative design of double\u2010layered drug coating on the surface of the biodegradable stent may provide therapeutic advantages over current treatment strategies for <jats:italic>P aeruginosa<\/jats:italic> sinusitis.<\/jats:p><\/jats:sec>","DOI":"10.1002\/alr.22514","type":"journal-article","created":{"date-parts":[[2019,12,23]],"date-time":"2019-12-23T22:26:26Z","timestamp":1577139986000},"page":"481-488","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Controlled delivery of ciprofloxacin and ivacaftor via sinus stent in a preclinical model of <i>Pseudomonas<\/i> sinusitis"],"prefix":"10.1002","volume":"10","author":[{"given":"Dong\u2010Jin","family":"Lim","sequence":"first","affiliation":[{"name":"Department of Otolaryngology\u2012Head &amp; Neck Surgery University of Alabama at Birmingham  Birmingham AL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6027-4976","authenticated-orcid":false,"given":"Justin","family":"McCormick","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2012Head &amp; Neck Surgery University of Alabama at Birmingham  Birmingham AL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Skinner","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2012Head &amp; Neck Surgery University of Alabama at Birmingham  Birmingham AL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaoyan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2012Head &amp; Neck Surgery University of Alabama at Birmingham  Birmingham AL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey B.","family":"Elder","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2012Head &amp; Neck Surgery University of Alabama at Birmingham  Birmingham AL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John G.","family":"McLemore","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2012Head &amp; Neck Surgery University of Alabama at Birmingham  Birmingham AL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Allen","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2012Head &amp; Neck Surgery University of Alabama at Birmingham  Birmingham AL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John Martin","family":"West","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2012Head &amp; Neck Surgery University of Alabama at Birmingham  Birmingham AL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2131-8005","authenticated-orcid":false,"given":"Jessica W.","family":"Grayson","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2012Head &amp; Neck Surgery University of Alabama at Birmingham  Birmingham AL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven M.","family":"Rowe","sequence":"additional","affiliation":[{"name":"Gregory Fleming James Cystic Fibrosis Research Center University of Alabama at Birmingham  Birmingham AL"},{"name":"Department of Medicine  University of Alabama at Birmingham  Birmingham AL"},{"name":"Department of Pediatrics University of Alabama at Birmingham  Birmingham AL"},{"name":"Department of Cell Developmental and Integrative Biology University of Alabama at Birmingham  Birmingham AL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bradford A.","family":"Woodworth","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2012Head &amp; 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