title: Prevention of sinonasal inflammation by a synthetic glycosaminoglycan.
abstract: Glycosaminoglycans (GAGs) are polysaccharides that are distributed on respiratory epithelial cells, endothelial cells, and submucosal glands. Uniquely positioned, certain GAGs exhibit anti-inflammatory properties in respiratory diseases and serve important roles in repairing mucosal surfaces and modulating mucociliary clearance. We hypothesized that topical administration of a synthetic GAG (GM-0111) would prevent sinonasal inflammation in a mouse model of rhinosinusitis (RS).
  
  
  
  To test our hypothesis, C57BL/6 mice were intranasally administered fluorescent GM-0111, and sinonasal tissues were examined for coating and penetration ability. To test therapeutic feasibility, mice (n = 6) were given GM-0111 or hyaluronic acid (HA; 800 μg dose) prior to inducing RS with inflammatory molecule LL-37 (115 μg dose). After 24 hours, sinonasal tissues were harvested for histological and biochemical analysis of inflammatory markers (inflammatory cell infiltration, lamina propria [LP] thickening, and neutrophil enzyme myeloperoxidase [MPO]) and cell death.
  
  
  
  GM-0111 was observed within sinonasal tissues 1 hour and 24 hours after intranasal administration, indicating rapid and effective coating and penetration. GM-0111 prevented sinonasal tissues from developing inflammatory changes, with significant reductions in mast cell infiltration (p < 0.05), LP thickening (p < 0.001), and MPO levels (p < 0.01) when compared to tissues treated with LL-37 and those pretreated with HA. GM-0111 reduced cell death within sinonasal tissues in contrast to LL-37-treated tissues.
  
  
  
  We report a new synthetic GAG (GM-0111) that uniformly coats and penetrates into the sinonasal mucosa to prevent sinonasal inflammation and cell death in a mouse model of RS.
authors.affiliation: Division of Head and Neck Surgery, Rhinology-Sinus and Skull Base Surgery Program, Department of Surgery; University of Utah School of Medicine, Salt Lake City, UT.|GlycoMira Therapeutics, Inc., Salt Lake City, UT.
authors.forename: Abigail
authors.initials: A
authors.lastname: Pulsipher
authors.affiliation: Division of Head and Neck Surgery, Rhinology-Sinus and Skull Base Surgery Program, Department of Surgery; University of Utah School of Medicine, Salt Lake City, UT.
authors.forename: Xuan
authors.initials: X
authors.lastname: Qin
authors.affiliation: Division of Head and Neck Surgery, Rhinology-Sinus and Skull Base Surgery Program, Department of Surgery; University of Utah School of Medicine, Salt Lake City, UT.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Thomas
authors.affiliation: Department of Medicinal Chemistry and Center for Therapeutic Biomaterials, Salt Lake City, UT.|GlycoMira Therapeutics, Inc., Salt Lake City, UT.
authors.forename: Glenn D
authors.initials: GD
authors.lastname: Prestwich
authors.affiliation: Department of Medicinal Chemistry and Center for Therapeutic Biomaterials, Salt Lake City, UT.|Division of Pediatric Urology, Department of Surgery, University of Utah School of Medicine, Salt Lake City, UT.
authors.forename: Siam
authors.initials: S
authors.lastname: Oottamasathien
authors.affiliation: Division of Head and Neck Surgery, Rhinology-Sinus and Skull Base Surgery Program, Department of Surgery; University of Utah School of Medicine, Salt Lake City, UT.|Department of Medicinal Chemistry and Center for Therapeutic Biomaterials, Salt Lake City, UT.
authors.forename: Jeremiah A
authors.initials: JA
authors.lastname: Alt
mesh_terms: D000287:Administration, Topical; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D016923:Cell Death / Q000187:drug effects; D004195:Disease Models, Animal; D006025:Glycosaminoglycans / Q000627:therapeutic use*; D006820:Hyaluronic Acid / Q000627:therapeutic use; D008297:Male; D008810:Mice, Inbred C57BL; D010256:Paranasal Sinuses / Q000473:pathology; D012852:Sinusitis / Q000188:drug therapy* / Q000473:pathology
chemical_list: D000893:Anti-Inflammatory Agents; D006025:Glycosaminoglycans; D006820:Hyaluronic Acid
keywords: anti-inflammatory therapeutic; cathelicidin; immune response; rhinosinusitis; sulfated glycosaminoglycan