Bovine serum albumin nanoparticles as a long-acting antiviral delivery platform for mycophenolic acid and ribavirin against emerging RNA viruses

Bovine serum albumin nanoparticles (BSA NP) encapsulating mycophenolic acid (MPA) and ribavirin (RBV) were developed as a sustained-release antiviral platform to address the limitations of conventional therapies against Zika (ZIKV) and Junín (JUNV) viruses. The BSA NP exhibited reproducible physicochemical properties, high drug loading efficiency, and excellent hemocompatibility (< 2% hemolysis). Cellular uptake studies revealed progressive internalization and prolonged intracellular retention, while antiviral assays demonstrated that encapsulated MPA and RBV maintained efficacy at 100- and 200-fold lower concentrations than their free forms, with activity lasting up to 96 h after a single dose. Furthermore, protein corona analysis with fibrinogen, albumin, and isoenzyme II showed how surface interactions influence NP stability and potential biodistribution. These findings are significant as they demonstrate that BSA represent a solid alternative to conventional treatments by sustaining intracellular levels and reducing systemic toxicity, offering a safe, biocompatible, and long-acting macromolecular platform for clinical antiviral applications. Overall, this study demonstrates that BSA-based NP constitute a non-immunogenic and effective long-acting delivery strategy that markedly enhances the intracellular exposure and antiviral performance of clinically validated broad-spectrum antivirals, supporting their potential as a solid alternative to conventional dosing regimens limited by toxicity and rapid clearance. In conclusion, BSA NPs represent a solid alternative to existing therapeutics by enhancing the therapeutic index of MPA and RBV, reducing systemic toxicity through controlled release, and providing a biocompatible platform for clinical antiviral applications.