© 2021 Elsevier B.V.Vaginal infections caused by various pathogens such as fungi, viruses and protozoa are frequently seen. Systemic and local treatments can be applied to eliminate these infections. Novel vaginal drug delivery systems can be used to provide local treatment. Vaginal drug delivery systems prevent systemic side effects and can provide long-term drug release in the vaginal area. Nanofibers and nanoparticles have a wide range of applications and can also be preferred as vaginal drug delivery systems. Benzydamine is a non-steroidal anti-inflammatory and antiseptic drug which is used for treatment of vaginal infections. The aim of this study was to compare the nanofiber and gel formulations containing lyophilized benzydamine nanoparticles with nanofiber and gel formulations containing free benzydamine, and to provide prolonged release for protection from the vaginal infections. Ionic gelation method was used for the preparation of benzydamine loaded nanoparticles. To produce benzydamine nanoparticles loaded nanofiber formulations, polyvinylpyrrolidone (PVP) solutions were prepared at 10% concentrations and mixed with nanoparticles. Hydroxypropyl methylcellulose (HPMC) was used as a gelling agent at the concentration of 1% for the vaginal gel formulation. Nanoparticles were characterized in terms of zeta potential, polydispersity index and particle size. Viscosity, surface tension and conductivity values of the polymer solutions were measured for the electrospinning. Mechanical properties, contact angle and drug loading capacity of the fibers were determined. Scanning electron microscopy (SEM), differential scanning calorimetry (DSC), transmission electron microscopy (TEM), fourier-transform infrared (FT-IR) spectroscopy, mucoadhesion, ex vivo permeability studies and in vitro release studies were performed for the selected formulations. Ex vivo permeability studies were performed using Franz diffusion cell method. SEM and TEM images showed that fiber diameters increased with loading of nanoparticles. DSC studies showed no interaction between excipients used in the formulation. Tensile strength and elongation at break values of the fibers increased with the loading of nanoparticles, and the contact angle values of the fibers were found to be 0°. Addition of benzydamine nanoparticles to gel and nanofiber formulations increased mucoadhesion compared to free benzydamine loading formulations. Benzydamine nanoparticle loaded gel and nanofiber formulations penetrated slower than that of free benzydamine gel and fiber formulations. The results demonstrated that benzydamine and benzydamine nanoparticle loaded fibers and gels could be a potential drug delivery system for the treatment of vaginal infections. Chitosan nanoparticle loaded nanofiber formulations are offered as an alternative controlled release vaginal formulations for vaginal infections.