Investigation of Migration-Preventing Tracheal Stent with High Dose of 5-Fluorouracil or Paclitaxel for Local Drug Delivery.

Stent migration is one of the common reasons for the failure of tracheal stent. An antitumor drug/tracheal stent combination can promptly relieve dyspnea caused by tracheal stenosis and locally treat malignant occupying lesion or tumor. To prevent stent migration for more effective treatment, we prepared a migration-preventing nitinol tracheal stent (TS) with a high dose of 5-fluorouracil or paclitaxel (5-FU/TS or PTX/TS) by stent surface coating with a bilayered film, which is composed of a drug-loaded layer containing Carbopol 974P as mucoadhesive matrix and a blank Carbopol 974P layer. The resulting stent had a similar mechanical performance with the nitinol tracheal stent itself. The bilayered film containing 30% PTX (PTX30) could keep adhesion to porcine mucosa for 221.7 ± 11.4 min in PBS at a stirring speed of 150 rpm, and the corresponding PTX30/TS was difficult to be moved in the porcine tracheal lumen with a pulling force less than 0.7 N, indicating its good migration-preventing ability. The migration-preventing ability of the 5-FU/TS or PTX/TS was related to the compositions of bilayered films. The 5-FU release from the 5-FU/TS was dominated by a relaxation mechanism, while the PTX release was mainly controlled by a diffusion mechanism. Moreover, the 5-FU permeation from the 5-FU loaded film through the porcine tracheal mucosa was determined by the 5-FU dissolution, and PTX permeation was limited by the trans-mucosa process. After the deployment of PTX30/TS, inflammatory responses were observed in the rabbit tracheas and gradually alleviated during the follow-up period.