Favipiravir (FVR) is a repurposed antiviral drug for treating mild to moderate cases of the novel coronavirus disease 2019 (COVID-19). However, its poor solubility and permeability limit its clinical efficacy. To overcome its physicochemical and pharmacokinetic limitations, we statistically designed a mucoadhesive chitosan-alginate nanoparticles (MCS-ALG-NPs) as a new carrier for FVR using response surface methodology, which provided suitable characteristics for transmucosal delivery. The use of mucoadhesive polymers for intranasal administration promotes the residence time and contact of FVR in the mucus membrane. The optimized FVR-MCS-ALG-NPs demonstrated superior mucoadhesion, higher permeation and deposition in the nasal mucosa, and a significant increase in the inhibition of viral replication over 35-fold compared with free FVR. The overall results suggest that MCS-ALG-NPs could be used as an effective mucoadhesive carrier to enhance the activity of FVR against COVID-19.
Keywords: Box–Behnken design; SARS-CoV-2; alginate; antiviral; chitosan; favipiravir; intra-nasal; polymeric nanoparticles; response surface methodology.