Basic Study
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jul 14, 2019; 25(26): 3370-3379
Published online Jul 14, 2019. doi: 10.3748/wjg.v25.i26.3370
Drug-eluting fully covered self-expanding metal stent for dissolution of bile duct stones in vitro
Chao Huang, Xiao-Bo Cai, Li-Li Guo, Xiao-Sheng Qi, Qiang Gao, Xin-Jian Wan
Chao Huang, Xiao-Bo Cai, Li-Li Guo, Xin-Jian Wan, Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 201620, China
Chao Huang, Xiao-Bo Cai, Li-Li Guo, Xin-Jian Wan, Shanghai Key Laboratory for Pancreatic Diseases, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 201620, China
Xiao-Sheng Qi, Department of General Surgery, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 201620, China
Qiang Gao, State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620, China
Author contributions: Huang C designed and mainly carried out all the experiments; Qi XS, Guo LL, and Gao Q assisted in carrying out the experiments; Wan XJ supervised the study; Huang C wrote the paper; Wan XJ together with Cai XB revised the article.
Supported by the National Natural Science Foundation of China, No. 81470904; and Shanghai Committee of Science and Technology, No. 14411963000.
Institutional review board statement: This study was approved by the Ethics Committee of Shanghai General Hospital, Shanghai Jiaotong University School of Medicine.
Institutional animal care and use committee statement: All experimental procedures were approved by the Animal Care and Use Committee of Shanghai Jiaotong University School of Medicine.
Conflict-of-interest statement: All authors declare no conflicts of interest related to this article.
Data sharing statement: No additional data are available.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Xin-Jian Wan, PhD, Chief Doctor, Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, No. 650, Xinsongjiang Road, Shanghai 201620, China. XinJian_Wan_shsy@163.com
Telephone: +86-21-6324-8460 Fax: +86-21-6324-8460
Received: April 25, 2019
Peer-review started: April 25, 2019
First decision: May 16, 2019
Revised: May 26, 2019
Accepted: May 31, 2019
Article in press: June 1, 2019
Published online: July 14, 2019
Processing time: 80 Days and 20.2 Hours
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; Fully covered self-expanding metal stent; Electrospinning; Nanofiber film

Core tip: The idea of delivering stone-dissolving agents to the location of common bile duct stones (CBDS) via biliary stent is first introduced by our research group. Based on our previous work and updated progress in the endoscopic field, we have further modified our previous version and present a brand-new stone-dissolving fully covered self-expanding metal stent, which is expected to serve as an alternative in the management of difficult CBDS.