A Methodological Pipeline for Investigating Efficacy and Toxicity of Topical Agents for the Treatment of CRS
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Authors List
Hale SJM, Lux CA, Broderick D, Biswas K, Kim R, Wagner Mackenzie B, Douglas RG Department of Surgery, Faculty of Medical and Health Sciences, University of Auckland Background: The sinonasal cavity is eminently suitable for the topical application of treatments for chronic rhinosinusitis (CRS), including agents for eradication of bacterial biofilms implicated in its pathogenesis and suppression of inflammation. We developed a model to investigate the efficacy of such agents in vitro and their toxicity to ciliated epithelium ex vivo, in order to identify those with potential for treating CRS. We have tested products containing polymyxin B, ethylenediaminetetraacetic acid, povidone-iodine, quaternary ammonium compounds, corticosteroids, and tyrosine kinase inhibitors. |
Dr Sam Hale, Registrar, Christchurch Hospital, Christchurch, NZ
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Methods: Biofilms of Staphylococcus aureus and Pseudomonas aeruginosa were grown in vitro using the Centers for Disease Control biofilm reactor and 96-pin lids. Time-kill and minimum biofilm eradication concentration assays, and scanning electron microscopy, were used to assess antibiofilm efficacy. An explant model was used to measure changes in gene expression following application of immune suppressants ex vivo. Agents were then applied to turbinectomy specimens collected from patients undergoing surgery for nasal obstruction, and changes in ciliary beat frequency were measured using cytobrush specimens taken from this tissue with high speed videomicroscopy.
Results: Consistent and repeatable measures of antibiofilm and anti-inflammatory efficacy were obtained. Ciliotoxicity testing provided clear discrimination between controls and test products.
Conclusions: We present a methodological pipeline by which topical agents may be assessed for efficacy and toxicity in vitro and ex vivo. This may facilitate future investigation of antibiofilm and anti-inflammatory agents with potential as novel topical therapies for CRS.
Results: Consistent and repeatable measures of antibiofilm and anti-inflammatory efficacy were obtained. Ciliotoxicity testing provided clear discrimination between controls and test products.
Conclusions: We present a methodological pipeline by which topical agents may be assessed for efficacy and toxicity in vitro and ex vivo. This may facilitate future investigation of antibiofilm and anti-inflammatory agents with potential as novel topical therapies for CRS.
