Niclosamide-Exfoliated Anionic Clay Nanohybrid Repurposed as an Antiviral Drug for Tackling Covid-19; Oral Formulation with Tween 60/Eudragit S100

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.

Orally administered niclosamide-based organic/inorganic hybrid suppresses SARS-CoV-2 infection

“…Identical absorption bands were also obtained from the as-made NIC-MgO-HPMC, which demonstrated the formation of broken π-π stacking interactions [38]. The greatest challenge in NIC delivery is its low aqueous solubility as previously reported by many researchers, including our group by repurposing technology using polymers [39,40] as well as inorganic clays [41].…”

“…The greatest challenge in NIC delivery is its low aqueous solubility as previously reported by many researchers, including our group by repurposing technology using polymers [39, 40] as well as inorganic clays [41].…”

Biomaterials Based on Organic Polymers and Layered Double Hydroxides Nanocomposites: Drug Delivery and Tissue Engineering

“…These results are superior to those data observed for the commercial form Yomesan ® : C max of about 155 ng/mL, t max of 4 h, and AUC of approximately 110 ng.h/mL. These results endorse the importance of using LDH to improve and combat diseases such as COVID-19 [ 212 ].…”

Bio-Inorganic Layered Double Hydroxide Nanohybrids in Photochemotherapy: A Mini Review

“…Therefore, stabilizing PCT agents inside the hybrids are of great relevance, which is critical to achieving an optimal therapeutic outcome. The interlayer nano-space and outer surface of clay NPs are highly functional since they are enriched with surface hydroxyl functional groups [ 35 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 ], which can easily be modified through covalent conjugation or hydrogen bonding. Some of the recent LDH-based inorganic hybrids are listed in Table 1 .…”

“…The application of clay-based NPs in PCT has several advantages because of their innate physicochemical functions, pore volume, internal surface properties, and structural and exchangeable cations [ 35 , 36 ]. The properties of these materials could be varied depending on the type of clay mineral and its structure.…”