title: Tolerance and pharmacokinetics of a ciprofloxacin-coated sinus stent in a preclinical model.
abstract: Chronic rhinosinusitis (CRS) is often associated with persistent bacterial infection despite the use of systemic antibiotics. Topically administered antibiotics are an alternative strategy, but require effective local concentrations, prolonged mucosal contact time, minor systemic absorption, and minimal depletion. The objectives of the current study were to analyze the in vitro release rate and in vivo drug delivery tolerance and pharmacokinetics of a ciprofloxacin-coated sinus stent (CSS).
  
  
  
  The CSS (2 mg) was created from biodegradable poly-D/L-lactic acid. After analyzing in vitro release profile, CSSs were placed unilaterally in maxillary sinuses of 16 rabbits via dorsal sinusotomy. Animals were euthanized between 1 and 3 weeks postoperatively. Ciprofloxacin concentrations in the sinus tissue and plasmas were assessed using high-performance liquid chromatography. Radiological and histological evaluations were performed.
  
  
  
  In the in vitro release profile, an initial burst release was observed over the first 24 hours, followed by sustained release through the 14-day time point. In the rabbit model, ciprofloxacin was continuously released from the stent up to 3 weeks at doses >50 ng/mL. Histologic examination found no evidence of inflammation, epithelial ulceration, or bony reaction upon euthanization of the animals at 21 days. Computed tomography also demonstrated no signs of mucosal edema or opacification in the sinus.
  
  
  
  The CSS was safe in this preclinical model and sustained release was observed in both the in vitro and in vivo analyses. The innovative stent design coated with ciprofloxacin may provide a unique therapeutic strategy for chronic rhinosinusitis (CRS).
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, University of Alabama at Birmingham, Birmingham, AL.|Gregory Fleming James Cystic Fibrosis Research Center, University of Alabama at Birmingham, Birmingham, AL.
authors.forename: Do-Yeon
authors.initials: DY
authors.lastname: Cho
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, University of Alabama at Birmingham, Birmingham, AL.
authors.forename: Kyle
authors.initials: K
authors.lastname: Hoffman
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, University of Alabama at Birmingham, Birmingham, AL.
authors.forename: Daniel
authors.initials: D
authors.lastname: Skinner
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, University of Alabama at Birmingham, Birmingham, AL.
authors.forename: Calvin
authors.initials: C
authors.lastname: Mackey
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, University of Alabama at Birmingham, Birmingham, AL.
authors.forename: Dong Jin
authors.initials: DJ
authors.lastname: Lim
authors.affiliation: Department of Biomedical Engineering, University of Alabama at Birmingham, Birmingham, AL.
authors.forename: Grant C
authors.initials: GC
authors.lastname: Alexander
authors.affiliation: Department of Biomedical Engineering, University of Alabama at Birmingham, Birmingham, AL.
authors.forename: Chae Yun
authors.initials: CY
authors.lastname: Bae
authors.affiliation: Center for Biomaterials, Korea Institute of Science and Technology (KIST), University of Science and Technology (UST), Seoul, South Korea.
authors.forename: Dong Keun
authors.initials: DK
authors.lastname: Han
authors.affiliation: Department of Biomedical Engineering, University of Alabama at Birmingham, Birmingham, AL.
authors.forename: Ho-Wook
authors.initials: HW
authors.lastname: Jun
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, University of Alabama at Birmingham, Birmingham, AL.|Gregory Fleming James Cystic Fibrosis Research Center, University of Alabama at Birmingham, Birmingham, AL.
authors.forename: Bradford A
authors.initials: BA
authors.lastname: Woodworth
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D002939:Ciprofloxacin / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D016503:Drug Delivery Systems; D065546:Drug Liberation; D054855:Drug-Eluting Stents; D005260:Female; D008443:Maxillary Sinus / Q000033:anatomy & histology / Q000000981:diagnostic imaging / Q000378:metabolism*; D011817:Rabbits; D020545:Respiratory Mucosa / Q000033:anatomy & histology / Q000000981:diagnostic imaging / Q000378:metabolism; D014057:Tomography, X-Ray Computed
chemical_list: D000900:Anti-Bacterial Agents; D002939:Ciprofloxacin
keywords: chronic sinusitis; ciprofloxacin; pharmacokinetics; rabbit; sinus stent; sinusitis; topical drug delivery