Controlled release of drugs is important to reduce the amount of medication in treatment of any diseases and improves life quality. Poly(e-caprolactone) (PCL) has a low biodegradation rate that is a disadvantage in the biomedical and pharmaceutical fields. Poly(N-vinyl-2-pyrrolidone) (PVP) is a water-soluble polymer that to overcome of PCL low biodegradation rate, electrospinning of PCL blended with PVP was used for shell of nanofibers with controllable degradation rates and drug release rates. Oral and vaginal mucosal infections mainly caused by candida albicans. It is usually a harmless commensal organism; however it is known as an opportunistic pathogen for almost immunologically week and immune compromised people. Amphotericin-B (AmB) is a strong polyene antifungal antibiotic that has a significantly efficacy on candida albicans. This study is manufactured and optimized the PVP-PCL shell/PVP-AmB core nanofiberous tissue by working distance and feed flow rate for controlled drug release. AmB with PVP was successfully inserted into the core. PVPPCL shell (50/50)/PVP-AmB core nanofiberous were electrospinning with two optimum distances working and two flow rates. The mechanical properties of coaxial nanofibers were analyzed by instron machine. Scanning electron microscopy and transmission electron microscopy was used for analysis morphology. Further, drug release test were done for coaxial nanofibers with AmB different morphologies. The effect of flow rate and working distance on morphology and mechanical properties were evaluated by statistical two-way analysis of the variance (ANOVA). The diameter averages of nanofibers were decreased significantly by increasing working distance. Moreover, the stress and strain were increased by increasing working distance. Coaxial nanofibers biodegradability rate and drug release of nanofibers were increased also by increasing working distance and flow rate of core. Nanofibers drug release mechanism was indicated by Korsmeyer-Peppas which they followed fick′s lows and Higuchi model significantly. Also, results presented that biodegradability and drug release rate accelerate with increasing the working distance and increasing the amount of PVP in core.