A novel core-shell structured nanofilm for the delivery of protein to the colon was developed by coaxial electrospinning using bovine serum albumin (BSA) as protein model. Firstly, the BSA-loaded chitosan nanoparticle was prepared by ionic gelation, and then the coaxial nanofilm was fabricated using alginate as shell layer and the BSA-loaded chitosan nanoparticle as core layer. Scanning electron microscopy analysis showed that the obtained nanofilm exhibited a smooth surface, and the core-shell structure was evidenced by the aid of transmission electron microscopy. There was little change in the secondary structure of encapsulated BSA and around 75% of BSA was released in the simulated colonic fluid. The corresponding kinetics models of BSA release in different simulated digestive fluids were built and the results revealed that the release of BSA in colon followed a complex mechanism. This study shows that electrospun nanofilm is a promising colon-specific delivery system for bioactive protein. (C) 2017 Elsevier Ltd. All rights reserved.