Niclosamide encapsulated in mesoporous silica and geopolymer: A potential oral formulation for COVID-19

Abstract

COVID-19 is a rapidly evolving emergency, for which there have been no specific medication found yet. Therefore, it is necessary to find a solution for this ongoing pandemic with the aid of advanced pharmaceutics. What is proposed as a solution is the repurposing of FDA approved drug such as niclosamide (NIC) having multiple pathways to inactivate the SARS-CoV-2, the specific virion that induces COVID-19. However, NIC is hardly soluble in an aqueous solution, thereby poor bioavailability, resulting in low drug efficacy. To overcome such a disadvantage, we propose here an oral formulation based on Tween 60 coated drug delivery system comprised of three different mesoporous silica biomaterials like MCM-41, SBA-15, and geopolymer encapsulated with NIC molecules. According to the release studies under a gastro/intestinal solution, the cumulative NIC release out of NIC-silica nanohybrids was found to be greatly enhanced to ∼97% compared to the solubility of intact NIC (∼40%) under the same condition. We also confirmed the therapeutically relevant bioavailability for NIC by performing pharmacokinetic (PK) study in rats with NIC-silica oral formulations. In addition, we discussed in detail how the PK parameters could be altered not only by engineered porous structure and property, but also by interfacial interactions between ion-NIC dipole, NIC–NIC dipoles and/or pore wall-NIC van der Waals in the intra-pores of silica nanoparticles.

Niclosamide-loaded nanoparticles disrupt Candida biofilms and protect mice from mucosal candidiasis

“…Our studies on the loading of NCL into NCL-E-PO-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 [59][60][61][62][63][64]. Remarkably, our investigation demonstrated, for the first time, high NCL loading in NPs due to strong interaction between NCL and EPO and at least 4 weeks of colloidal stability of NCL-EPO-NP.…”

Repurposing Anthelmintics: Rafoxanide- and Copper-Functionalized SBA-15 Carriers against Methicillin-Resistant Staphylococcus aureus

“…9−13 To this end, recently, there has been more research aimed at investigating the effect of salicylanilide anthelmintic drugs such as rafoxanide (RFX), 14,15 niclosamide, 16−19 and closantel 17 against Gram-positive and Gram-negative bacteria. Most recently, tests of this family of drugs (anthelmintics) against viruses like COVID-19 20 and some forms of cancer 21−25 have also been performed.…”

“…Such nanosystems could also be more suitable to incorporate into antimicrobial formulations. 20 or Pluronic 123), with an average molecular mass of ∼5800, was donated by BASF. Tetraethyl orthosilicate (TEOS), Cu(II) acetate (Cu(CH 3 COO) 2 ), hydrochloric acid (HCl) solution (37%), and absolute ethanol (99.99%) were purchased from Fischer Scientific.…”

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

“…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.…”