Development of molnupiravir and peramivir loaded liposome formulations for combined antiviral therapy

The pandemic caused by the SARS-CoV-2 virus has led scientists to intensify research on antiviral drugs and vaccines. As a result of these studies, it was observed that molnupiravir (MLP) and peramivir (PRV) could be used against pandemic. MLP affects SARS-CoV-2 replication, but it necessitates high doses, which can cause adverse effects in patients. PRV is a neuraminidase inhibitor, but the bioavailability of the drug after oral administration is very low. In this study, MLP-, PRV-loaded and combined liposome (COMB-Lipo) formulations were prepared via the thin film hydration method. Phospholipon 90 G-based formulations exhibited the most favorable characteristics, with a particle size of 111-145 nm, a polydispersity index (PDI) of less than 0.4, and a zeta potential (ZP) of 6-12 mV). Cell culture studies demonstrated that developed stable formulations are nontoxic to L929 and Vero E6 cells. Antiviral activity assessments against SARS-CoV-2 suggested the effectiveness of liposomes in inhibiting viral activity. These findings demonstrate that a possible synergistic effect of the newly developed sustained-release COMB-Lipo formulation is suggested with the complementary antiviral mechanisms of the combined agents. As a result, the therapeutic potential of co-delivery of anti-SARS-CoV-2 drugs for pulmonary application is considered a promising approach for long-acting treatment of COVID-19.