Paclitaxel-eluting self-extending metal stent for palliative therapy of unresectable cholangiocarcinoma

초록

Objectives Recently introduced nonvascular metal stents provide excellent therapeutic efficacy for the obstructive symptoms of benign or malignant GI stricture. However, recurrent restenosis remains a major concern, especially for malignant tumors such as cholangio carcinoma. In this study, we designed and evaluated a paclitaxel-eluting nanofiber membrane (PTX-ESM)-covered stent for palliative therapy of GI tumors. Methods A two-layered PTX-eluting membrane was designed. Silicon primary membrane which can polarize the release of PTX to the tumoral side and enhance the mechanical strength of membrane was applied as a backing layer. PTX and polyurethane (PU) were electrospun on the top of the silicon layer. In vitro characteristics and in vivo antitumor efficacies were evaluated as follows. Results SEM study showed that nanofiber less than 1 μm of diameter was layered on the primary membrane. PTX released in controlled manner for more than 30 days. Compared with the subtumoral injection of PTX solution (Genexol-PM®), PTX-ESM significantly inhibited the growth of CT-26 murine colon cancer. LC-MSMS analysis showed that PTX maintained higher local concentrations over 1.0 μg/ml at tumor for more than 14 days without systemic exposure. Histology (TUNEL and H&E staining) also indicated that locally concentrated PTX induced the higher level of apoptosis than systemic injection. Conclusions This study suggests that PTX-eluting nonvascular stent possibly inhibits the in-growth of tumor and extends the patency of non-vascular stent. Clinical feasibility of PTX-eluting nanofiber-nonvascular stent for cholangiocarcinoma and GI tumors will be investigated in further studies.