Drug-eluting fully covered self-expanding metal stent for dissolution of bile duct stones in vitro

World J Gastroenterol. 2019 Jul 14;25(26):3370-3379. doi: 10.3748/wjg.v25.i26.3370.

Abstract

Background: The treatment of difficult common bile duct stones (CBDS) remains a big challenge around the world. Biliary stenting is a widely accepted rescue method in patients with failed stone extraction under endoscopic retrograde cholangiopancreatography. Fully covered self-expanding metal stent (FCSEMS) has gained increasing attention in the management of difficult CBDS.

Aim: To manufacture a drug-eluting FCSEMS, which can achieve controlled release of stone-dissolving agents and speed up the dissolution of CBDS.

Methods: Customized covered nitinol stents were adopted. Sodium cholate (SC) and disodium ethylene diamine tetraacetic acid (EDTA disodium, EDTA for short) were used as stone-dissolving agents. Three different types of drug-eluting stents were manufactured by dip coating (Stent I), coaxial electrospinning (Stent II), and dip coating combined with electrospinning (Stent III), respectively. The drug-release behavior and stone-dissolving efficacy of these stents were evaluated in vitro to sort out the best manufacturing method. And the selected stone-dissolving stents were further put into porcine CBD to evaluate their biosecurity.

Results: Stent I and Stent II had obvious burst release of drugs in the first 5 d while Stent III presented controlled and sustainable drug release for 30 d. In still buffer, the final stone mass-loss rate of each group was 5.19% ± 0.69% for naked FCSEMS, 20.37% ± 2.13% for Stent I, 24.57% ± 1.45% for Stent II, and 33.72% ± 0.67% for Stent III. In flowing bile, the final stone mass-loss rate of each group was 5.87% ± 0.25% for naked FCSEMS, 6.36% ± 0.48% for Stent I, 6.38% ± 0.37% for Stent II, and 8.15% ± 0.27% for Stent III. Stent III caused the most stone mass-loss no matter in still buffer or in flowing bile, which was significantly higher than those of other groups (P < 0.05). In vivo, Stent III made no difference from naked FCSEMS in serological analysis (P > 0.05) and histopathological examination (P > 0.05).

Conclusion: The novel SC and EDTA-eluting FCSEMS is efficient in diminishing CBDS in vitro. When conventional endoscopic techniques fail to remove difficult CBDS, SC and EDTA-eluting FCSEMS implantation may be considered a promising alternative.

Keywords: Common bile duct stone; Drug-eluting stent; Electrospinning; Fully covered self-expanding metal stent; Nanofiber film.

MeSH terms

  • Alloys
  • Animals
  • Common Bile Duct
  • Disease Models, Animal
  • Drug Carriers / chemistry
  • Drug Liberation
  • Drug-Eluting Stents*
  • Edetic Acid / administration & dosage*
  • Edetic Acid / pharmacokinetics
  • Gallstones / therapy*
  • Humans
  • Male
  • Nanofibers
  • Polyesters / chemistry
  • Self Expandable Metallic Stents*
  • Sodium Cholate / administration & dosage*
  • Sodium Cholate / pharmacokinetics
  • Swine
  • Swine, Miniature
  • Treatment Outcome

Substances

  • Alloys
  • Drug Carriers
  • Polyesters
  • polycaprolactone
  • nitinol
  • Edetic Acid
  • Sodium Cholate