This study investigates the use of a modified coaxial electrospinning process in the production of drug-loaded cellulose acetate (CA) nanofibers. With CA employed as a filament-forming matrix and ketoprofen (KET) as an active pharmaceutical ingredient, modified coaxial processes using sheath fluids comprising only mixed solvents were undertaken. With a sheath-to-core flow rate ratio of 0.2:1, the nanofibers prepared from the coaxial process had a smaller average diameter, narrower size distribution, more uniform structures, and smoother surface morphologies than those generated from single fluid electrospinning. In addition, the coaxial fibers provided a better zero-order drug release profile. The use of a sheath solvent means that the core jet is subjected to electrical drawing for a longer period, facilitating homogeneous core jet solidification and retarding the formation of wrinkles on the surface of the nanofibers. This modified coaxial electrospinning protocol allows the systematic fabrication of functional polymer nanofibers with improved quality. (C) 2012 Elsevier Ltd. All rights reserved.