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SNJ Pharma, Inc

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Int. J. Antimicrob. Agents, 21 September 2023, 106973 | https://doi.org/10.1016/j.ijantimicag.2023.106973 Oral delivery of a host-directed antiviral, niclosamide, with the cholate-coated nanoformulation

Chongkai Zhai ^a,b,1, Mingda Wang^a,1, Yanyan Jin ^c,1, Hea-Jong Chung^d,1, Sura Kim ^a, Hyeon-Jin Kim ^e, Seong-Tshool Hong ^a

^aDepartment of Biomedical Sciences and Institute for Medical Science, Jeonbuk National University Medical School, Jeonju, Jeonbuk 54907, South Korea

^bAnimal Diseases and Public Health Engineering Research Center of Henan Province, Luoyang Polytechnic, Luoyang, China

^cDepartment of Respiratory and Critical Care Medicine, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, China

^dGwangju Center, Korea Basic Science Institute, Gwangju 61751, South Korea

^eSNJ Pharma Inc., BioLabs-LA at the Lundquist Institute for BioMedical Innovation at Harbor UCLA, Torrance, CA 90502, USA

¹The author contributed equally.

Corresponding authors: Hyeon-Jin Kim, Seong-Tshool Hong

Abstract

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.

논문정보

형식Research article
게재일2023년 09월 (BRIC 등록일 2023-10-04)
연구진국내(교신)+국외 연구진
분야 생명과학 > 미생물학

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