External sheath has been suggested for autologous vein grafts to inhibit neointimal hyperplasia and prevent anastomosis stricture. In this study, we prepared a bi-layer biodegradable paclitaxel-loaded sheaths with a synthetic copolymer poly(ethylene carbonate-epsilon-caprolactone) at room temperature. The bi-layer drug release profiles of the Paclitaxel-loaded (PTX-loaded) sheath significantly slow down the paclitaxel (PTX) release rates and result in a directional drug release way. Moreover, the nanofibrous layer of PTX-loaded poly(EC-CL) sheaths reduced the cytotoxicity and provided a better support for fibroblast adhesion and proliferation than the PTX-loaded layer of the sheaths. Thus, this study demonstrates that the bi-layer PTX-loaded poly(EC-CL) sheath with directional drug release profiles have a promising application for vein graft to against neointimal hyperplasia and anastomotic stricture. (C) 2013 Elsevier B. V. All rights reserved.