title: Safety evaluation of a sinus surfactant in an explant-based cytotoxicity assay.
abstract: OBJECTIVE
  Biofilms are associated with clinical relapse following surgery for chronic rhinosinusitis. Encased bacteria are protected from innate immunity and antimicrobial therapy. Surfactants can disperse the biofilm into its planktonic phenotype so that traditional treatments may be effective. The aim of this study was to assess a surfactant for its cytotoxicity profile.
  
  
  METHODS
  In vitro explant-based cytotoxicity study.
  
  
  METHODS
  Sinonasal mucosa harvested from patients undergoing sinus surgery was tested using an air-liquid interface explant system. Surfactant at 1×, 2×, and 3× manufacturer's recommended concentrations were compared to control (saline) and Zinc Sulphate (ZnSO4 ), a known cytotoxic agent. Culture supernatant was analyzed for lactate dehydrogenase (LDH) as a marker of cellular toxicity. After 7 days, specimens were imaged using structured histopathology and scanning electron microscopy.
  
  
  RESULTS
  Application of surfactant at 1× concentration did not elicit an elevation in LDH, whereas ZnSO4 caused a significant rise 1 day after application. Specimens tested with a 2× and 3× surfactant demonstrated LDH rises 4 days and 2 days after application, respectively. Mucosa tested with the 1× surfactant and control demonstrated intact cellular structures on histopathology and preserved cilial ultrastructure on SEM. In ZnSO4 -treated specimens, marked cellular degradation and ciliary denudation occurred.
  
  
  CONCLUSIONS
  The surfactant does not appear to elicit cellular toxicity using an in vitro explant model at the manufacturer's recommended concentration. At higher concentrations, there may be dose-related toxicity that requires further investigation. In vivo testing is required to prove its efficacy in the treatment of recalcitrant chronic rhinosinusitis.
  
  
  METHODS
  N/A.
authors.affiliation: Department of Surgery-Otolaryngology, University of Adelaide, Adelaide, Australia.
authors.forename: Neil C-W
authors.initials: NC
authors.lastname: Tan
authors.forename: Clare M
authors.initials: CM
authors.lastname: Cooksley
authors.forename: Sathish
authors.initials: S
authors.lastname: Paramasivan
authors.forename: Sarah
authors.initials: S
authors.lastname: Vreugde
authors.forename: Peter-John
authors.initials: PJ
authors.lastname: Wormald
mesh_terms: D018441:Biofilms / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D009297:Nasal Mucosa / Q000166:cytology* / Q000187:drug effects* / Q000648:ultrastructure; D010256:Paranasal Sinuses / Q000648:ultrastructure; D013501:Surface-Active Agents / Q000633:toxicity*
chemical_list: D013501:Surface-Active Agents
keywords: Chronic rhinosinusitis; biofilm; cytotoxicity; human sinonasal explants; sinus surfactant