We have developed a novel drug delivery system with the swelling core for differential release of multiple drugs by emulsion electrospinning, in which the aqueous phase is composed of polyvinyl alcohol and the oil phase consists of poly(epsilon-caprolactone). The microscopy images indicate that the W/O nanofibers with swelling core structure are successfully prepared and the model drugs, Rhodamine B and bovine serum albumin, were encapsulated in the fibers. In vitro drug release study demonstrated that this core-sheath structure could significantly alleviate the initial drug burst release and provided a differential diffusion pathway to release. It could be found that the postponement of the maximum accumulated release of bovine serum albumin was found due to the presence of sodium citrate and different types of polyvinyl alcohol. This study would provide a basis for optimization of encapsulation conditions to control the release of multiple agents and ultimately be applied in cancer chemotherapy. (C) 2014 Elsevier B.V. All rights reserved.