A series of drug-incorporating electrospun biocompatible nanofibers were fabricated by using the electrospinning process. A hydrophobic drug (ibuprofen, IBU) was directly dissolved with biopolymer systems such as polyvinyl alcohol/plasma modified chitosan (PVA/PMCh), polyvinyl alcohol/chitosan (PVA/Ch) and cellulose acetate (CA) into an organic solvent prior to electrospinning. The release of IBU from drug-loaded electrospun fibers was monitored using a quartz crystal microbalance (QCM). The results were compared with utilizing UV/Vis spectroscopy results. The biocompatible fibers were Fourier transform infrared spectroscopy (FTIR). The IBU-loaded PVA/Ch and PVA/PMCh fibers demonstrated more effective and uniform release profiles than the IBU-loaded CA fibers.