Polymeric delivery systems using electrospun nanofibers have been developed for many applications, notably for drug delivery and tissue engineering in the healthcare industry. In this study, a nanofiber drug carrier was fabricated via two different electrospinning processes, blend and coaxial, using a new degradable thermoplastic carboxymethyl cellulose (TCMC) and poly(ethylene oxide) (PEO). The TCMC was synthesized by graft copolymerization with methyl acrylate. Tetracycline hydrochloride served as a drug model incorporated within these nanofibers and their performance as a drug-carrier scaffold was evaluated. The structure morphology of the obtained nanofibers was viewed under scanning electron microscope, and the changes of the structural of polymer before and after graft and confirmation of incorporation of the drug on the fibers was characterized by Fourier transform infrared spectroscopy. Response surface methodology was applied to predict the optimum condition for fabrication of the nanofibers. The drug-delivery profile showed that drug release from the optimized core shell sample TCMC 3% (w/v)/PEO 1% (w/v) was much slower than for the blend nanofibers and was sustained for 72 h with only 26.06% burst release within the first 30 min. The drug-loaded TCMC 3% (w/v)/PEO 1% (w/v) core-shell sample nanofibers showed excellent bactericidal activity against a wide range of bacteria, indicating their potential as antibacterial materials in various applications such as tissue engineering and pharmaceutical science. (C) 2017 Elsevier B.V. All rights reserved.