Preclinical evaluation of new indomethacin-eluting biodegradable urethral stent

J Endourol. 2012 Apr;26(4):387-92. doi: 10.1089/end.2011.0327. Epub 2012 Jan 4.

Abstract

Purpose: 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.

Materials and 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.

Conclusion: 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.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biocompatible Materials / pharmacology*
  • Biodegradation, Environmental / drug effects
  • Cell Line
  • Cytokines / biosynthesis
  • Drug Evaluation, Preclinical
  • Drug-Eluting Stents*
  • Humans
  • Indomethacin / pharmacology*
  • Lactic Acid / chemistry
  • Lipopolysaccharides / pharmacology
  • Male
  • Microscopy, Electron, Scanning
  • Polyesters
  • Polyglycolic Acid / chemistry
  • Polymers / chemistry
  • Rabbits
  • Urethra / drug effects*
  • Urethra / pathology

Substances

  • Biocompatible Materials
  • Cytokines
  • Lipopolysaccharides
  • Polyesters
  • Polymers
  • Polyglycolic Acid
  • Lactic Acid
  • poly(lactide)
  • Indomethacin