Development of mucoadhesive polymeric nanoparticles for intranasal delivery of Favipiravir in treating SARS-CoV-2 infection

Abstract

Nanoparticles (NPs) have been used as an effective carrier for transmucosal delivery of drugs through their prolonged residence time and deposition, or the enhanced permeation through the mucosa. In this study, we aimed to design a nanocarrier using the combined mucoadhesive (M) properties of chitosan (CS) and alginate (ALG) polymers for the intranasal delivery of favipiravir (FVR) in treating SARS-CoV-2 infection. The optimized FVR-loaded mucoadhesive CS-coated ALG-NPs (FVR-MCS-ALG-NPs) rendered suitable size (233.5 nm), zeta potential (-21.6 mV), loading capacity (26.0%), and encapsulation efficiency (84.6%) for transmucosal delivery. Superior mucoadhesiveness and higher permeation and deposition in the porcine nasal mucosa of the FVR-MCS-ALG-NPs over uncoated-NPs (3-fold) and free FVR (6-fold) were observed. Both NP formulations rendered good biocompatibility in RPMI 2650 nasal epithelial cell and porcine nasal mucosa. Significant inhibition of coronavirus replication was also observed in the FVR-MCS-ALG-NPs vs free FVR (EC50 6.63 vs >230 μg/mL, respectively) suggesting a promising carrier for FVR to enhance its antiviral activity and deposition in the nasal mucosa.