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 CPCOV03 (NIC–MgO–HPMC), a nanohybrid formulation of niclosamide designed to overcome 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 nano-niclosamide formulations. The absence of systemic toxicities validates CPCOV03 as a scalable and biocompatible therapeutic platform suitable for extended dosing regimens. By combining durable safety with enhanced drug performance, CPCOV03 holds strong translational potential for treating persistent viral infections, such as long COVID, and for oncology applications. • Nanoengineered formulation: CPCOV03 (NIC–MgO–HPMC) integrates magnesium oxide nanoparticles with hydroxypropyl methylcellulose to overcome niclosamide’s poor solubility, stability, and bioavailability. • Safe-by-design approach: Developed with a rational design framework to maximize pharmacological performance while minimizing long-term risks. • Comprehensive 13-week in vivo evaluation: Toxicology assessed across hepatic, renal, and hematologic systems. • Excellent safety profile: No abnormalities observed in clinical signs, serum biochemistry, hematology, or histopathology of major organs. • Long-term tolerability established: First foundational benchmark confirming the biocompatibility of nano-niclosamide for chronic use. • Translational relevance: Scalable, safe platform with strong potential in persistent viral infections (e.g., long COVID) and oncology applications requiring extended dosing.