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

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.

Antibiotic eluting sinus stents

“…The initial burst release observed in the CSS is a well-documented phenomenon among stent therapy including the SESS, which showed 90% of drug release over the first 13 days. 50,58,59 Prior studies have shown that hydrophobic molecules loaded onto nanoparticles, as opposed to hydrophilic molecules such as ciprofloxacin, exhibit more sustained release over time. 58 It was thus hypothesized that developing a two layered stent with an inner, hydrophilic ciprofloxacin coating and an outer, hydrophobic drug would control the burst-release phenomenon.…”

The degradable performance of bile‐duct stent based on a continuum damage model: A finite element analysis

“…The biliary system has the function of secreting, storing, concentrating and transporting bile, but the incidence of biliary obstruction, including the benign biliary obstruction caused by bile duct injury and recurrent cholangitis or congenital scar constriction of bile duct cavity, and the malignant biliary obstruction caused by bile duct liver cancer, pancreatic cancer and metastatic cancer, is high. Endoscopically placed bile duct stents are commonly used for the treatment of pancreaticobiliary disorders, 1,2 biliary stenting is also a widely accepted rescue method in patients with failed stone extraction under endoscopic retrograde cholangiopancreatography 3 …”

“…Most bile duct stents are small tubular scaffolds. However, not everyone can accept long‐term stent placement because of the complications of bile duct stent release, such as stent slipping and migration, infection and foreign body reactions, perforation of the bile duct, and recurrent stenosis due to cholestasis 1,3‐5 . Therefore, many stents consisting of bio‐absorbable metals, such as magnesium (Mg) or iron (Fe) and their alloys, appeared and have the potential to address limitations in the current generation of permanent stents 6,7 .…”

3D Printed Model of Extrahepatic Biliary Ducts for Biliary Stent Testing

“…Efficient and accurate in vitro testing of these devices during pre-clinical studies, in lieu of large animal testing, reduces the number of research animals that undergo procedures and/or are sacrificed to obtain the pre-clinical data required for submission to the FDA [4][5][6]. To date, in vitro Materials 2020, 13, 4788 2 of 11 studies of biliary stents have been performed in systems that do not mimic the anatomy and/or the mechanical properties of the EHBD [7][8][9][10].…”

“…Herein, we describe our efforts to fabricate an anatomically accurate EHBD model with Formlabs 3D printers and polymers for in vitro biliary stent testing. studies of biliary stents have been performed in systems that do not mimic the anatomy and/or the mechanical properties of the EHBD [7][8][9][10]. The EHBDs are comprised of the common bile duct (CBD), cystic duct, common hepatic duct (CHD), left hepatic duct (LHD), and right hepatic duct (RHD).…”