Gut and Liver Safety Evaluation of Paclitaxel-Eluting Biliary Metal Stent with Sodium Caprate in Porcine Biliary Tract
Author Information
Sung Ill Jang1, Seok Jeong2,3, Don Haeng Lee2,3, Kun Na4, Sugeun Yang5, and Dong Ki Lee1
1 Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, 2 Department of Internal Medicine, Inha University Hospital, Inha University College of Medicine, 3 Utah-Inha DDS & Advanced Therapeutics Research Center, Incheon, 4 Department of Biotechnology, The Catholic University of Korea, Bucheon, and 5 Department of New Drug Development and World Class Smart Lab, Inha University College of Medicine, Incheon, Korea

Dong Ki Lee (https://orcid.org/0000-0002-0048-9112)a and Sugeun Yang (https://orcid.org/0000-0001-5278-8723)b
aDepartment of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, 211 Eonju-ro, Gangnam-gu, Seoul 06273, Korea
Tel: +82-2-2019-3214, Fax: +82-2-3463-3882, E-mail: dklee@yuhs.ac
bDepartment of New Drug Development and World Class Smart Lab, Inha University College of Medicine, 100 Inha-ro, Michuhol-gu, Incheon 22212, Korea
Tel: +82-32-890-2832, Fax: +82-32-890-1199, E-mail: sugeun.yang@inha.ac.kr
© The Korean Society of Gastroenterology, the Korean Society of Gastrointestinal Endoscopy, the Korean Society of Neurogastroenterology and Motility, Korean College of Helicobacter and Upper Gastrointestinal Research, Korean Association the Study of Intestinal Diseases, the Korean Association for the Study of the Liver, Korean Pancreatobiliary Association, and Korean Society of Gastrointestinal Cancer. All rights reserved.

Abstract
Background/Aims: Metallic stents designed to relieve malignant biliary obstruction are susceptible to occlusive tumor ingrowth or overgrowth. In a previous report, we described metallic stents covered with paclitaxel-incorporated membrane (MSCPM-I, II) to prevent occlusion from tumor ingrowth via antitumor effect. This new generation paclitaxeleluting biliary stent is further endowed with sodium caprate (MSCPM-III) for enhanced drug delivery. The purpose of this study is to examine the safety of its drug delivery system in the porcine biliary tract. Methods: MSCPM-III (10% [wt/vol] paclitaxel) and covered metal stents (CMSs) were endoscopically inserted in porcine bile ducts in vivo. Histologic biliary changes, levels of paclitaxel released, and various serum analytes (albumin, alkaline phosphate, aspartate transaminase, alanine transaminase, total protein, total bilirubin, and direct bilirubin) were assessed. Results: Based on the intensity of reactive inflammation and fibrosis, changes in porcine biliary epithelium secondary to implanted MSCPMIII were deemed acceptable (i.e., safe). Histologic features in the MSCPM-III and CMS groups did not differ significantly. In a related serum analysis, paclitaxel release from MSCPMIII stents was below the limit of detection for 28 days. Biochemical analyses were also similar for the two groups, and no evidence of hepatic or renal toxicity was found in animals receiving MSCPM-III stents. Conclusions: In a prototypic porcine trial, this newly devised metal biliary stent incorporating both paclitaxel and sodium caprate appears to be safe in the porcine bile duct.
Keywords: Drug-eluting stent; Self expandable metallic stent; Drug delivery systems; Biliary tract neoplasms; Pancreatic neoplasm
Abstract
Background/Aims: Metallic stents designed to relieve malignant biliary obstruction are susceptible to occlusive tumor ingrowth or overgrowth. In a previous report, we described metallic stents covered with paclitaxel-incorporated membrane (MSCPM-I, II) to prevent occlusion from tumor ingrowth via antitumor effect. This new generation paclitaxeleluting biliary stent is further endowed with sodium caprate (MSCPM-III) for enhanced drug delivery. The purpose of this study is to examine the safety of its drug delivery system in the porcine biliary tract. Methods: MSCPM-III (10% [wt/vol] paclitaxel) and covered metal stents (CMSs) were endoscopically inserted in porcine bile ducts in vivo. Histologic biliary changes, levels of paclitaxel released, and various serum analytes (albumin, alkaline phosphate, aspartate transaminase, alanine transaminase, total protein, total bilirubin, and direct bilirubin) were assessed. Results: Based on the intensity of reactive inflammation and fibrosis, changes in porcine biliary epithelium secondary to implanted MSCPMIII were deemed acceptable (i.e., safe). Histologic features in the MSCPM-III and CMS groups did not differ significantly. In a related serum analysis, paclitaxel release from MSCPMIII stents was below the limit of detection for 28 days. Biochemical analyses were also similar for the two groups, and no evidence of hepatic or renal toxicity was found in animals receiving MSCPM-III stents. Conclusions: In a prototypic porcine trial, this newly devised metal biliary stent incorporating both paclitaxel and sodium caprate appears to be safe in the porcine bile duct.
Keywords: Drug-eluting stent; Self expandable metallic stent; Drug delivery systems; Biliary tract neoplasms; Pancreatic neoplasm
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