Translational potential of safe-by-design nanoengineered niclosamide in viral and cancer therapy

This study presents a comprehensive evaluation of the long-term biocompatibility of CP-COV03 (NIC-MgO-HPMC), a nanohybrid formulation of niclosamide designed to overcome its limitations in solubility, stability, and bioavailability. Developed under a safe-by-design framework, NIC-MgO-HPMC integrates magnesium oxide (MgO) nanoparticles with hydroxypropyl methylcellulose (HPMC) to enhance pharmacological performance while ensuring safety for chronic use. Over a 13-week in vivo exposure period, the toxicological profile was systematically assessed, focusing on hepatic, renal, and hematologic systems. Clinical observations, serum biochemistry, and hematology revealed no abnormalities at clinically relevant dosages. Histopathological examination of major organs confirmed the absence of tissue damage or structural alterations, underscoring the nanohybrid's long-term tolerability. These findings establish the first foundational safety benchmark for chronic use of nanoengineered niclosamide hybrids. The absence of systemic toxicities validates CP-COV03 as a scalable and biocompatible therapeutic platform suitable for extended dosing regimens. By combining durable safety with enhanced drug performance, CP-COV03 offers strong translational potential for persistent viral infections, including long COVID, future pandemic threats, and oncology applications.