Preclinical efficacy and safety of novel SNAT against SARS-CoV-2 using a hamster model

Abstract

To address the unprecedented global public health crisis due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), we designed and developed a novel antiviral nano-drug, called SNAT (Smart Nano-Enabled Antiviral Therapeutic), comprised of taxoid (Tx)-decorated amino (NH 2 )-functionalized near-atomic size positively charged silver nanoparticles (Tx–[NH 2 -AgNPs]) that are stable for over 3 years. Using a hamster model, we tested the preclinical efficacy of inhaled SNAT on the body weight, virus titer, and histopathology of lungs in SARS-CoV-2-infected hamsters, including biocompatibility in human lung epithelium and dermal fibroblasts using lactase dehydrogenase (LDH) and malondialdehyde (MDA) assays. Our results showed SNAT could effectively reverse the body weight loss, reduce the virus load in oral swabs, and improve lung health in hamsters. Furthermore, LDH assay showed SNAT is noncytotoxic, and MDA assay demonstrated SNAT to be an antioxidant, potentially quenching lipid peroxidation, in both the human cells. Overall, these promising pilot preclinical findings suggest SNAT as a novel, safer antiviral drug lead against SARS-CoV-2 infection and may find applications as a platform technology against other respiratory viruses of epidemic and pandemic potential. Graphical abstract Supplementary information The online version contains supplementary material available at 10.1007/s13346-022-01166-x.

Nanoparticles for Antimicrobial Agents Delivery—An Up-to-Date Review

“…Nanodimensional materials, such as metallic NPs, metal-oxide NPs, lipid-based NPs, and polymeric NPs, have attracted considerable interest in recent years for fabricating delivery vehicles. Specifically, the variety and versatility of nanomaterials have been extensively explored by researchers for creating innovative therapeutic formulations that can be administrated on different routes, including oral [2,141,142], ocular [82,83,143], intranasal [125,129,130], intratracheal [55,144], intravaginal [145,146], intravesical [147,148], and transdermal [149,150] routes. Compared to free drugs, NP-loaded antimicrobial agents can be administered in so many ways due to their increased safety, reduced systemic adverse effects, enhanced solubility, and improved bioavailability.…”

“…Taking into account the benefits of NPs, several research studies explored the antimicrobial potential of a number of antiviral drugs encapsulated in different nanomaterials. Examples of investigated nanocarriers include silver NPs [125], titanium dioxide NPs [126], oligo-and polysaccharide-based NPs [127][128][129][130][131], solid lipid NPs (SLNs) [132,133], and large unilamellar vesicles [134]. The ingenious association with antivirals (e.g., docetaxel [125], flavonoids [126], zidovudine [127,128], dolutegravir sodium [129], efavirenz [130], acyclovir [131,132], ritonavir [133]) and functionalization agents has led to the obtaining of promising anti-infective therapeutic nanoformulations.…”

“…Examples of investigated nanocarriers include silver NPs [125], titanium dioxide NPs [126], oligo-and polysaccharide-based NPs [127][128][129][130][131], solid lipid NPs (SLNs) [132,133], and large unilamellar vesicles [134]. The ingenious association with antivirals (e.g., docetaxel [125], flavonoids [126], zidovudine [127,128], dolutegravir sodium [129], efavirenz [130], acyclovir [131,132], ritonavir [133]) and functionalization agents has led to the obtaining of promising anti-infective therapeutic nanoformulations. Specifically, the proposed delivery systems targeted clinically relevant viruses, such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) [125,126], HIV [127][128][129][130][133][134][135], and HSV [131,132].…”