title: Preclinical evaluation of new indomethacin-eluting biodegradable urethral stent.
abstract: OBJECTIVE
  To evaluate the effect of an indomethacin-eluting biodegradable urethral stent on the production of inflammatory cytokines in vitro and the degradation and biocompatibility of the new stent in vivo.
  
  
  METHODS
  The effects of an indomethacin and indomethacin-eluting biodegradable stent on monocyte chemoattractant protein (MCP)-1, RANTES (regulated on activation, normal T-cell expressed and secreted), and transforming growth factor-ß were measured in THP-1 cells by enzyme-linked immunosorbent assay. Stents (copolymer of L-lactide and glycolide acid) that were coated with 50L/50D polylactic acid and two different concentrations of indomethacin were inserted into the rabbit urethra. Stents without the drug were used as controls. Scanning electron microscopy (SEM) was used to assess the degradation of the stents. Biocompatibility was evaluated using histologic analyses of the urethral specimen. The measurements were performed at 3 weeks and 3 months.
  
  
  RESULTS
  Indomethacin and indomethacin-releasing stent material inhibited MCP-1 and RANTES production in activated THP-1 macrophages. SEM analysis revealed that indomethacin coating had no effect on the degradation process of the stents and less epithelial polyposis had developed in the indomethacin stent group. In histologic analyses at 3 weeks, indomethacin-eluting stents caused more calcification but no significant differences in other tissue reactions. At 3 months, the indomethacin-eluting stents caused less inflammatory reaction and calcification compared with the control stents.
  
  
  CONCLUSIONS
  Indomethacin-eluting property can be safely added to biodegradable stents without major influence on the degradation time. The development of epithelial polyposis in the urethra can be potentially reduced by the new indomethacin-eluting urethral stents.
authors: Department of Urology, Tampere University Hospital, Teiskontie 35, Tampere, Finland. andres.kotsar@fimnet.fi
authors: Andres
authors: A
authors: Kotsar
authors: Riina
authors: R
authors: Nieminen
authors: Taina
authors: T
authors: Isotalo
authors: Joonas
authors: J
authors: Mikkonen
authors: Ilkka
authors: I
authors: Uurto
authors: Minna
authors: M
authors: Kellomäki
authors: Martti
authors: M
authors: Talja
authors: Eeva
authors: E
authors: Moilanen
authors: Teuvo L J
authors: TL
authors: Tammela
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000494:pharmacology*; D001673:Biodegradation, Environmental / Q000187:drug effects; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis; D004353:Drug Evaluation, Preclinical; D054855:Drug-Eluting Stents; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology*; D019344:Lactic Acid / Q000737:chemistry; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D008855:Microscopy, Electron, Scanning; D011091:Polyesters; D011100:Polyglycolic Acid / Q000737:chemistry; D011108:Polymers / Q000737:chemistry; D011817:Rabbits; D014521:Urethra / Q000187:drug effects* / Q000473:pathology
chemical_list: D001672:Biocompatible Materials; D016207:Cytokines; D008070:Lipopolysaccharides; D011091:Polyesters; D011108:Polymers; D011100:Polyglycolic Acid; D019344:Lactic Acid; C033616:poly(lactide); D007213:Indomethacin