title: Halofuginone-coated urethral catheters prevent periurethral spongiofibrosis in a rat model of urethral injury.
abstract: OBJECTIVE
  Urethral strictures are from periurethral spongiofibrosis that develops as a result of urethral trauma, disease, or iatrogenic injury. The spongy tissue that surrounds the strictured urethra has an altered ratio of collagen, with increased collagen type I relative to type III. We evaluated the ability of a urethral catheter that was coated with halofuginone (HF), a potent type I collagen inhibitor, to prevent spongiofibrosis formation in a rat model.
  
  
  METHODS
  HF was coated on silicone catheters and release kinetics were measured. Success of impregnation was evaluated with scanning electron microscopy, serial weights, and drug elution data. Urethral strictures were induced in rats using electrocautery. Half the animals had placement of an HF-coated catheter while the others had uncoated silicone controls. Animals were sacrificed at predetermined time points, and urethral tissue was either processed for staining with Masson trichrome and anti-alpha-1 collagen or digested to determine HF concentration. Serum drug levels were also determined in treated animals. Slides were graded by a pathologist who was blinded to treatment to determine collagen deposition.
  
  
  RESULTS
  HF was coated successfully on silicone catheters. Local urethral concentration of HF was tenfold higher than serum concentration in treated rats. Animals with HF-coated catheters had no new type I collagen deposition after urethral injury. Control animals had increased periurethral collagen type I deposition, typical of urethral stricture formation.
  
  
  CONCLUSIONS
  HF can be coated successfully on silicone catheters. HF successfully inhibits periurethral type I collagen deposition after urethral injury. This may become an important therapy to prevent urethral stricture formation or recurrence after endoscopic therapy.
authors.affiliation: Department of Urology, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157, USA.
authors.forename: Louis S
authors.initials: LS
authors.lastname: Krane
authors.forename: Ilya
authors.initials: I
authors.lastname: Gorbachinsky
authors.forename: Joseph
authors.initials: J
authors.lastname: Sirintrapun
authors.forename: James J
authors.initials: JJ
authors.lastname: Yoo
authors.forename: Anthony
authors.initials: A
authors.lastname: Atala
authors.forename: Steve J
authors.initials: SJ
authors.lastname: Hodges
mesh_terms: D000818:Animals; D057785:Catheters; D002921:Cicatrix / Q000473:pathology; D024042:Collagen Type I / Q000378:metabolism; D004195:Disease Models, Animal; D008297:Male; D010880:Piperidines / Q000097:blood / Q000494:pharmacology*; D052999:Quinazolinones / Q000097:blood / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013194:Staining and Labeling; D015607:Stents; D014521:Urethra / Q000187:drug effects* / Q000473:pathology; D014522:Urethral Diseases / Q000473:pathology / Q000517:prevention & control*
chemical_list: D024042:Collagen Type I; D010880:Piperidines; D052999:Quinazolinones; C010176:halofuginone