Safety Evaluation of Paclitaxel-Eluting Biliary Metal Stent with Sodium Caprate in Porcine Biliary Tract

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 paclitaxel-eluting 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 MSCPM-III 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 MSCPM-III 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.

An exploratory research on antitumor effect of drug-eluting slow-releasing electrospinning membranes

“…PTX-eluting covered bile stents, may represent a potential strategy for preventing occlusion due to tumor growth and further inhibiting tumor development. The biosafety of metal stents covering PTX has been reported in recent years [ 14 , 19 ]. Yuan et al [ 20 ] compared the efficacy and safety of PTX-eluting metal stents (PECMS), metallic stents covered with a PTX-incorporated membrane (MSCPM), and conventional covered metal stents (CMS) in the treatment of malignant biliary obstruction.…”

A review on biodegradable biliary stents: materials and future trends

“…Jang et al also obtained promising results following the safety evaluation of a drug delivery system in the porcine biliary tract, whereby a metal stent covered with paclitaxel membrane (MSCPM-III) was implanted. But they also reported that there was no significant difference in stent patency and patient survival between the MSCPM group and the control group [ 53 , 54 ]. In addition to PTX, there are other drugs that could potentially inhibit biliary stricture, such as gemcitabine, rapamycin, and mitomycin-C. Gemcitabine is the standard chemotherapy drug used to treat advanced pancreatic cancer and cholangiocarcinoma.…”