Abstract
COVID-19 has been affecting millions of individuals worldwide and, thus far, there is no accurate therapeutic strategy. This critical situation necessitates novel formulations for already existing, FDA approved, but poorly absorbable drug candidates, such as niclosamide (NIC), which is of great relevance. In this context, we have rationally designed NIC-loaded hydrotalcite composite nanohybrids, which were further coated with Tween 60 or hydroxypropyl methyl cellulose (HPMC), and characterized them in vitro. The optimized nanohybrids showed particle sizes <300 nm and were orally administrated to rats to determine whether they could retain an optimum plasma therapeutic concentration of NIC that would be effective for treating COVID-19. The pharmacokinetic (PK) results clearly indicated that hydrotalcite-based NIC formulations could be highly potential options for treating the ongoing pandemic and we are on our way to understanding the in vivo anti-viral efficacy sooner. It is worth mentioning that hydrotalcite–NIC nanohybrids maintained a therapeutic NIC level, even above the required IC50 value, after just a single administration in 8–12 h. In conclusion, we were very successfully able to develop a NIC oral formulation by immobilizing with hydrotalcite nanoparticles, which were further coated with Tween 60 or HPMC, in order to enhance their emulsification in the gastrointestinal tract.
Highlights
COVID-19 has been affecting millions of individuals globally, leaving lives miserable, especially in under-developed countries and even in poor areas of cities in advanced countries [1]
COVID-19 is typically affected by SARS-CoV-2 virus, and is highly transmissible compared to previous variants, such as MERS and SARS [2,3,4], which previously affected
Schematic diagram of (a) the preparation of designed NIC–dehydrated HT (DHT) nanohybrid and (b) NIC–DHT coated with Tween 60 or hydroxypropyl methyl cellulose (HPMC) through a physical adsorption reaction
Summary
COVID-19 has been affecting millions of individuals globally, leaving lives miserable, especially in under-developed countries and even in poor areas of cities in advanced countries [1]. COVID-19 is typically affected by SARS-CoV-2 virus, and is highly transmissible compared to previous variants, such as MERS and SARS [2,3,4], which previously affected. [5] Though the number of cases are increasing all around the world, and vaccinations have started globally, actual therapy for COVID-19 remains onerous to many scientists. SARS-CoV-2, among which niclosamide (NIC) is of great importance. Wu et al [6] and Gassen et al [7] reported that NIC can inhibit the viral replication of SARS-CoV and MERS-CoV, respectively. A very recent study revealed that NIC had Pharmaceuticals 2021, 14, 486.
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