Oral delivery of a host-directed antiviral, niclosamide, with the cholate-coated nanoformulation.

Potentially significant drug candidates often face elimination from consideration due to the lack of an effective method for systemic delivery. The poor solubility of these candidates has posed a major obstacle for their development as oral pills or injectables. Niclosamide, a host-directed antiviral, would be the best example. In this study, we have developed a nanoformulation technology that allows for the non-covalent formulation of niclosamide with cholic acids. This formulation enables efficient systemic delivery through the endocytosis and enterohepatic circulation of the bile acid-coated nanoparticles. The oral bioavailability of the niclosamide-delivery nanoparticle (NDN) was significantly enhanced to 38.3%, representing an eight-fold increase compared to pure niclosamide. Consequently, the plasma concentration of niclosamide in the NDN formulation reached up to 1,179.6 ng/mL, which is eleven times higher than the therapeutic plasma level. This substantial increase in plasma levels contributed to the complete resolution of clinical symptoms in animals infected with SARS-CoV-2. Our nanoformulation not only provides an orally deliverable antiviral drug for SARS-CoV-2 with improved pharmaceutical bioavailability but also offers a solution to the systemic delivery challenges faced by potentially significant drug candidates.Copyright © 2023. Published by Elsevier Ltd.

Citation

Chongkai Zhai, Mingda Wang, Yanyan Jin, Hea-Jong Chung, Sura Kim, Hyeon-Jin Kim, Seong-Tshool Hong. Oral delivery of a host-directed antiviral, niclosamide, with the cholate-coated nanoformulation. International journal of antimicrobial agents. 2023 Sep 21:106973106973

PMID: 37741586

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