Development of niclosamide-based COVID-19 therapeutic agent using porous silicon nanoparticles

Abstract This study explores the potential of porous silicon nanoparticles (pSiNPs) as advanced nanocarriers to enhance the therapeutic efficacy and reduce the cytotoxicity of niclosamide for coronavirus disease 2019 (COVID-19) treatment. Niclosamide, an FDA-approved drug used to treat tapeworm infections, has been suggested as a potential treatment for COVID-19. However, its clinical application is limited by its significant cytotoxicity and low bioavailability. To address these challenges, three types of pSiNPs—pSiNP-H, pSiNP-COOH, and pSiNP-NH ₂ —were synthesized. Niclosamide was successfully loaded onto each type of pSiNPs, achieving a loading efficiency over 30%. Among them, the antiviral activity of niclosamide-loaded pSiNP-NH ₂ was assessed against the Delta variant of Severe acute respiratory syndrome coronavirus 2 in Vero E6 cells using plaque assays and real-time PCR. Results demonstrated that niclosamide-loaded pSiNP-NH ₂ significantly suppressed viral replication more efficiently than free niclosamide at equivalent doses, while minimizing host cell cytotoxicity. These findings suggest that pSiNP-NH ₂ could serve as a potent drug delivery platform, improving the therapeutic index of niclosamide for COVID-19 treatment.