PURPOSE: The present study aimed to develop and compare the intranasal applicability of favipiravir-loaded aspasomes (FAV-ASPs) using film hydration method, and favipiravir-loaded niosomes (FAV-NIOs) using ethanol injection method. METHODS: The FAV-ASP and FAV-NIO formulations were characterized according to nanoparticulate characteristics (DLS, drug loading, drug encapsulation efficacy, droplet size distribution), drug release and permeability behavior. RESULTS: The optimized FAV-ASP formulation (FAV-ASP8) consisted of FAV, ascorbyl palmitate, Span® 60 and cholesterol (30:25:25:50 w/w) with nano-scale size range (292.06 ± 2.10 nm), narrow polydispersity index (PDI) value (0.36 ± 0.03), adequate zeta potential (-74.73 ± 3.28 mV) and acceptable encapsulation efficiency (55.33 ± 0.41%). The optimized FAV-NIO formulation (FAV-NIO9) contained FAV, Span® 60 and cholesterol (30:30:40 ) with nano-scale size range (167.13 ± 1.60 nm), narrow PDI value (0.07 ± 0.01), adequate zeta potential (-27.1 ± 1.24 mV) and acceptable encapsulation efficiency (51.30 ± 0.69%). FAV-ASP8 and FAV-NIO9 were suitable for spraying into the nasal cavity (droplet size distribution <200 µm). In vitro drug release and permeability studies demonstrated enhanced solubility and increased blood-brain barrier (BBB) permeability of FAV formulations, respectively. The ex vivo human nasal permeability study revealed that FAV diffusion from FAV-ASP8 was higher than from FAV-NIO9 or initial FAV. Furthermore, the in vivo animal study showed that FAV-ASP8 had a higher BBB penetration compared to FAV-NIO9 and pure FAV. The in vitro-in vivo correlation study showed good correlation between the in vitro and the in vivo pharmacokinetic data. CONCLUSION: FAV-ASP8 for nose-to-brain delivery system could be a promising formulation to improve FAV bioavailability compared to FAV-NIO9.