Hydrotalcite–Niclosamide Nanohybrid as Oral Formulation towards SARS-CoV-2 Viral Infections

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.

Bovine Serum Albumin-Coated Niclosamide-Zein Nanoparticles as Potential Injectable Medicine against COVID-19

“…For example, NIC was made into a PEGylated injectable formulation by Ma et al (2019), though there was no information provided regarding the actual particle size and morphology of the developed injectable NIC formulation [48]. Recently, our group reported new oral formulations for NIC, showing excellent PK results compared with many other related studies [26].…”

“…Although NIC has very high anti-viral efficacy, the major drawback is its extremely poor water solubility, which thereby limits the in-vivo efficacy [25]. There have been various methodologies proposed, such as physical and chemical modification, to alter the pharmacokinetics (PK) of NIC, as suggested recently by our research group [23,26]. However, in general, one has to be very careful when selecting an appropriate drug delivery carrier for the repurposing applications.…”

“…Though there are different kinds of drug carriers reported for NIC formulations, such as inorganic montmorillonite (MMT), dehydrotalcite (DHT) [23,26], and chitosan [33], here we chose Zein, a biocompatible phytoprotein, mainly because it is highly biocompatible and degradable and it has been extensively studied for various biomedical applications [34][35][36][37][38][39]. In addition, there are several reports suggesting that Zein-based hybrids are well-tolerated for human applications.…”

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

“…Male Sprague-Dawley rats, ~0.3 kg in weight, were used for PK analysis as per previous protocols (Choi et al, 2021a;Yu et al, 2021), which were sanctioned by the Institutional Animal Care and Use Committee (IACUC No. IA21-00816) at Korea Conformity Laboratories (Incheon, Korea).…”

Niclosamide loaded Eudragit EPO nanoparticles show enhanced Candida biofilm penetration, trigger biofilm detachment and protect from mucosal candidiasis

“…Our studies on the loading of NCL into NCL-EPO-NPs revealed a possibility of significantly higher NCL loading into NCL-EPO-NPs (NCL: EPO ratio 4:10 or 40% w/w of EPO) without compromising its size and colloidal stability. Interestingly, hitherto reported NCL nanoformulations involving use of materials such as natural polysaccharides (chitosan and xylan), solid lipids, inorganic materials such as mesoporous silica and hallocyte and biodegradable polymers such as polylactide-co-glycolide (PLGA) to load NCL, were unable to achieve NCL loading > 10% and none of these reports evaluated long-term colloidal stability of NCL nanoformulations [60][61][62][63][64][65] .…”