The present study reports zero-order controlled release drug-loaded nanofibers fabricated using a modified coaxial electrospinning, in which a 2% (w/v) dilute solution of polyacrylonitrile (PAN) was exploited as a sheath fluid. With PAN and acyclovir (ACY) as the filament-forming matrix and active pharmaceutical ingredient, respectively, the prepared nanofibers had linear morphologies and clear core-shell structures, as verified by electron microscopic observations. X-ray diffraction tests demonstrated that ACY presented in the PAN matrix in an amorphous status. In vitro dissolution tests showed that near 80% of the contained ACY in the nanofibers was freed in a zero-order manner without initial burst effect.