Background: Biliary metallic stents are covered with a membrane to prevent tumor ingrowth and to prolong patency. The only function of these stents is to promote biliary drainage; they have no antitumor effect.
Methods: A metallic stent was developed that is covered with a paclitaxel-incorporated membrane. The metallic stents were coated with one of 3 concentrations of paclitaxel (0, 10, and 20 % wt/v) and polyurethane. A stent with each concentration was surgically inserted in the bile duct of two pigs. Four weeks after insertion, the segment of bile duct containing the stent was examined histologically. To determine the efficacy of the drug release, stents were placed in phosphate buffered saline solution for 6 weeks, and the amount of paclitaxel released was measured by high-performance liquid chromatography.
Results: The histologic changes in the pig biliary epithelium were acceptable with respect to safety and included inflammatory cell infiltration and fibrous reactions. The changes corresponded to the amount of paclitaxel incorporated within the stent in contact with the bile duct. Epithelial denudation, mucin hypersecretion, and epithelial metaplasia were noted in the bile ducts that were in contact with stents containing 20 % wt/v paclitaxel. Transmural necrosis and perforation were not observed in any animal. In the in vitro experiment, the amounts of paclitaxel released over 1 week and over 6 weeks were similar, regardless of the concentration of paclitaxel incorporated in the stent. The stent with 10% (wt/v) paclitaxel in the covering membrane was found to be better than that with 20 % (wt/v) with respect to histologic changes and the effectiveness of drug release.
Conclusions: A paclitaxel-incorporated metallic stent could serve as a basis for the development of a new and safe treatment modality for malignant biliary obstruction. Clinical trials of this stent with other adjuvant therapy are warranted.