In this work, electrospinning was used to fabricate core-shell nanofibers containing acid-base pairs. Quercetin was used as a model active ingredient. To exploit its solubility in basic conditions, a solution of quercetin, polyvinylpyrrolidone (PVP) and sodium hydroxide was used as the core fluid, and one consisting of citric acid and PVP as the shell fluid. Scanning and transmission electron microscopy demonstrated that core-shell nanofibers with linear morphologies were obtained, without beads or spindles. X-ray diffraction showed that quercetin was present in the fibers in an amorphous state; Fourier transform infrared spectroscopy indicated this may be a result of hydrogen bonding between the drug and the polymer matrix. In in vitro dissolution tests the drug was found to be released immediately when the fibers encountered an aqueous medium. There was no change in the pH of the medium after dissolution, as a result of the presence of the acid-base pair. This provides a new strategy for improving the dissolution behavior of poorly water-soluble drugs using polymeric nanostructures.