The effect on porcine bile duct of a metallic stent covered with a paclitaxel-incorporated membrane.
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.
Lee
Dong Ki
DK
Kim
Hyun Soo
HS
Kim
Kyung-Sik
KS
Lee
Woo Jung
WJ
Kim
Ho Keun
HK
Won
Young Hyun
YH
Byun
Young Ro
YR
Kim
Moon Young
MY
Baik
Soon Koo
SK
Kwon
Sang Ok
SO
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage*; D001652:Bile Ducts / Q000473:pathology; D016503:Drug Delivery Systems; D004867:Equipment Design; D008567:Membranes, Artificial; D017239:Paclitaxel / Q000008:administration & dosage*; D015607:Stents; D013552:Swine
D000972:Antineoplastic Agents, Phytogenic; D008567:Membranes, Artificial; D017239:Paclitaxel