A facile and efficient protocol for the preparation of nanofibers incorporating polymeric ketoprofen prodrugs and polyvinylpyrrolidone was developed. Polymeric ketoprofen prodrugs were constructed by a two-step chemo-enzymatic synthetic route, and nanofibers prepared by electrospinning from dimethylformamide/ethanol (1 : 1, v/v) solutions. The morphological characteristics of the fibers were influenced by the concentration of active agent in the spinning solution; average diameters varied from 196 to 370 nm. In vitro release studies indicated that the ketoprofen release rate from the electrospun fibers was significantly higher than that from the pure polymeric prodrugs. Cumulative drug release from the electrospun fibers reached 40-70% after 3 h and 75-100% after 12 h, while the pure polymeric prodrug released only 7-9% of the active agent over 12 h. Functional nanofibers incorporating polymeric prodrugs therefore comprise potentially effective drug delivery systems for sustained release. (c) 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 130: 1570-1577, 2013