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 the 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.