NICLOSAMIDE-EXFOLIATED ANIONIC CLAY NANOHYBRID REPURPOSED AS AN ANTIVIRAL DRUG FOR TACKLING COVID-19; ORAL FORMULATION WITH TWEEN 60/EUDRAGIT S100

N Sanoj Rejinold; Huiyan Piao; Goeun Choi; Geun-Woo Jin; Jin-Ho Choy

doi:10.1007/s42860-021-00153-6

NICLOSAMIDE-EXFOLIATED ANIONIC CLAY NANOHYBRID REPURPOSED AS AN ANTIVIRAL DRUG FOR TACKLING COVID-19; ORAL FORMULATION WITH TWEEN 60/EUDRAGIT S100

Clays Clay Miner. 2021;69(5):533-546. doi: 10.1007/s42860-021-00153-6. Epub 2021 Nov 11.

Authors

N Sanoj Rejinold¹, Huiyan Piao¹, Goeun Choi^{1

2

3}, Geun-Woo Jin⁴, Jin-Ho Choy^{1

5

6}

Affiliations

¹ Intelligent Nanohybrid Materials Laboratory (INML), Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan, 31116 Korea.
² College of Science and Technology, Dankook University, Cheonan, 31116 Korea.
³ Department of Nanobiomedical Science and BK21 PLUS NBM Global Research Centre for Regenerative Medicine, Dankook University, Cheonan, 31116 Korea.
⁴ R&D Centre, CnPharm Co., LTD., Seoul, 03759 Korea.
⁵ Department of Pre-medical Course, College of Medicine, Dankook University, Cheonan, 31116 Korea.
⁶ Tokyo Tech World Research Hub Initiative (WRHI), Institute of Innovative Research, Tokyo Institute of Technology, Yokohama, 226-8503 Japan.

Abstract

The ongoing pandemic, COVID-19 (SARS-CoV-2), has afflicted millions of people around the world, necessitating that the scientific community work, diligently and promptly, on suitable medicaments. Although vaccination programs have been run globally, the new variants of COVID-19 make it difficult to restrict the spread of the virus by vaccination alone. The combination of vaccination with anti-viral drug formulation is an ideal strategy for tackling the current pandemic situation. Drugs approved by the United States Food and Drug Administration (FDA), such as Remdesivir, have been found to be of little or no benefit. On the other hand, re-purposing of FDA-approved drugs, such as niclosamide (NIC), has offered promise but its applicability is limited due to its poor aqueous solubility and, therefore, low bioavailability. With advanced nano-pharmaceutical approaches, re-purposing this drug in a suitable drug-carrier for a better outcome may be possible. In the current study, an attempt was made to explore the loading of NIC into exfoliated layered double hydroxide nanoparticles (X-LDH NPs); prepared NIC-X-LDH NPs were further modified with eudragit S100 (ES100), an enteric coating polymer, to make the final product, ES100-NIC-X-LDH NPs, to improve absorption by the gastro/intestinal tract (GIT). Furthermore, Tween 60 was added as a coating on ES100-NIC-X-LDH NPs, not just to enhance its in vitro and in vivo stability, but also to enhance its mucoadhesive property, and to obtain, ultimately, better in vivo pharmacokinetic (PK) parameters upon oral administration. Release of NIC from Tween 60-ES100-NIC-X-LDH NPs was found to be greater under gastro/intestinal solution within a shorter period of time than the uncoated samples. The in vivo analysis revealed that Tween 60-ES100-NIC-X-LDH NPs were able to maintain a therapeutically relevant NIC plasma concentration in terms of PK parameters compared to the commercially available Yomesan®, proving that the new formulation might prove to be an effective oral drug-delivery system to deal with the SARS-CoV-2 viral infections. Further studies are required to ensure their safety and anti-viral efficacy.

Supplementary information: The online version contains supplementary material available at 10.1007/s42860-021-00153-6.

Keywords: COVID-19; Exfoliated layered double hydroxide nanoparticles; Niclosamide; Oral formulation; Pharmacokinetics.