For the purpose of achieving targeted chemotherapy of pancreatic cancer, we prepared core-shell nanoparticles by coaxial electrospray technology, with folate-chitosan as the polymeric coating material and gemcitabine as the encapsulated drug. The effects of various solution properties and processing parameters on nanoparticles formation were investigated. By optimizing the electrospray parameters, the diameter of the core-shell nanoparticles was in the range of 200-300 nm with drug loading and encapsulation efficiency of 3.91 +/- 0.12% and 85.37 +/- 4.9%. The drug release kinetics revealed a controlled initial burst release followed by a sustained release over a period of 72 h at pH 7.4 and pH 5.0, and at pH 5.0 the drug released more quickly. Moreover, the cellular uptake experiment confirmed that the folate conjugated core-shell nanoparticles had high pancreatic cancer (BXPC3) cells uptake efficiency. And the cell cytotoxicity test displayed that they had remarkable cytotoxicity towards BXPC3 cells. This study indicates that coaxial electrospray is a facile technique in producing core-shell nanoparticles encapsulating hydrophilic small molecule drugs, and clearly infers that the folate conjugated core-shell nanoparticles is very much effective to use as a pancreatic tumor-targeted delivery carrier for anticancer drugs.