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bioRxiv · 10.1101/2025.11.10.687694

Enhanced Zika Virus Suppression by Coupling Ribavirin with Biodegradable Drug Delivery

Rodriguez, J.·Waterman, A.·Blahove, M. R.·Saviskas, J.·Santos-Villalobos, B.·Wallace, M.·Carter, J.
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Abstract

Advancement and implementation of nanoparticle-based systems for enhanced drug delivery have become essential for the suppression of viral pathogens due to lack of viable treatment options. This study focuses on characterization and application of mPEG-PCL co-polymers for development of pH-responsive, biodegradable micellar nanoparticles (MNPs) for the delivery of the antiviral drug ribavirin against Zika virus. Synthesis of mPEG-PCL diblock copolymers was confirmed through FTIR and 1H NMR, which validated the formation of ester functional groups and accurate structure of copolymers. mPEG-PCL MNPs, loaded with ribavirin, exhibited a mean diameter of approximately 34.29 {+/-} 5.214 nm and a zeta potential of -3.28 {+/-} 0.718 mV, suitable for evading immune detection and facilitating cellular entry. The ribavirin-loaded mPEG-PCL MNPs demonstrated pH-dependent release, with approximately 88% of ribavirin released at pH 5.5, compared to 20% at pH 7.4. This pH-responsive release is crucial for targeted drug delivery within the endosomal pathway. In vitro studies using JEG-3 cells infected with Zika virus showed that ribavirin-loaded mPEG-PCL MNPs achieved an EC50 of 0.22nM, significantly enhancing drug efficacy compared to unencapsulated ribavirin, which required micromolar concentrations to achieve similar effects. The MTT assay results indicated minimal cytotoxicity of the ribavirin-loaded mPEG-PCL MNPs, with approximately 80% cell viability at the highest concentration evaluated. Confocal microscopy and RT-PCR analysis further confirmed the efficient cellular uptake and potent antiviral activity of the ribavirin-loaded MNPs. These findings highlight the potential of mPEG-PCL MNPs as an effective delivery system for broad-spectrum antivirals like ribavirin, enhancing their therapeutic efficacy while minimizing cytotoxicity.

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Rodriguez, J., Waterman, A., Blahove, M. R., Saviskas, J., Santos-Villalobos, B., Wallace, M., Carter, J.. 2025-11-11. Enhanced Zika Virus Suppression by Coupling Ribavirin with Biodegradable Drug Delivery. https://doi.org/10.1101/2025.11.10.687694

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