Repurpose but also (nano)-reformulate! The potential role of nanomedicine in the battle against SARS-CoV2

Abstract

The coronavirus disease-19 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) has taken the world by surprise. To date, a worldwide approved treatment remains lacking and hence in the context of rapid viral spread and the growing need for rapid action, drug repurposing has emerged as one of the frontline strategies in the battle against SARS-CoV2. Repurposed drugs currently being evaluated against COVID-19 either tackle the replication and spread of SARS-CoV2 or they aim at controlling hyper-inflammation and the rampaged immune response in severe disease. In both cases, the target for such drugs resides in the lungs, at least during the period where treatment could still provide substantial clinical benefit to the patient. Yet, most of these drugs are administered systemically, questioning the percentage of administered drug that actually reaches the lung and as a consequence, the distribution of the remainder of the dose to off target sites. Inhalation therapy should allow higher concentrations of the drug in the lungs and lower concentrations systemically, hence providing a stronger, more localized action, with reduced adverse effects. Therefore, the nano-reformulation of the repurposed drugs for inhalation is a promising approach for targeted drug delivery to lungs. In this review, we critically analyze, what nanomedicine could and ought to do in the battle against SARS-CoV2. We start by a brief description of SARS-CoV2 structure and pathogenicity and move on to discuss the current limitations of repurposed antiviral and immune-modulating drugs that are being clinically investigated against COVID-19. This account focuses on how nanomedicine could address limitations of current therapeutics, enhancing the efficacy, specificity and safety of such drugs. With the appearance of new variants of SARS-CoV2 and the potential implication on the efficacy of vaccines and diagnostics, the presence of an effective therapeutic solution is inevitable and could be potentially achieved via nano-reformulation. The presence of an inhaled nano-platform capable of delivering antiviral or immunomodulatory drugs should be available as part of the repertoire in the fight against current and future outbreaks.

The Importance of Nanocarrier Design and Composition for an Efficient Nanoparticle-Mediated Transdermal Vaccination

“…This is how vaccines such as Pfizer and BioNTech RNA: BNT162b2 and modern mRNA-1273 based on purified messenger RNA are used today [137,138]. Although these designs are administered parenterally, without a doubt, they open the door to the development of new technologies, aiming at needle-free vaccination and is not only limited to the transport of antigens but also undoubtedly an open door towards the development of new therapies for the treatment of COVID-19 [139].…”

Chitosan and its derivatives as polymeric anti-viral therapeutics and potential anti-SARS-CoV-2 nanomedicine

“…Clinically, the efficacy of many other drugs such as arbidol, baricitinib, camostat mesilate, darunavir, lopinavir, nafamostat mesilate, oseltamivir, recombinant human angiotensin converting enzyme 2, recombinant interferon-α2β, interferon-β1, ribavirin and ritonavir as well as immunomodulatory drugs such as ravulizumab, ruxolitinib, sarilumab and sirolimus have been evaluated against SARS-CoV-2 ( Murugan et al, 2021 ; Tammam et al, 2021 ). Solid lipid nanoparticles, nanostructured lipid carriers, nanoemulsion, polymeric nanoparticles, metallic nanoparticles, dendrimer, PEGylated cationic liposome, immunoliposome, carbon dots and carbon nanotubes are examples of nanocarrier developed for the delivery of anti-viral drugs ( Shah et al, 2021 ).…”

“…Solid lipid nanoparticles, nanostructured lipid carriers, nanoemulsion, polymeric nanoparticles, metallic nanoparticles, dendrimer, PEGylated cationic liposome, immunoliposome, carbon dots and carbon nanotubes are examples of nanocarrier developed for the delivery of anti-viral drugs ( Shah et al, 2021 ). Nanoformulation of such drugs is envisaged to bring about the following critical advantages: increased drug solubility, prolonged drug residence/circulation time, reduced off-target drug exposure, sustained drug retention or transportation across biological barriers, flexibility in downstream delivery system design, decoratable with targeting ligand for effective binding to host cells and virus, enhanced cellular uptake particularly by the immune cells, and nanoscale geometry sufficient to restrict virus mobility and block its fusion with host ( Al-Hatamleh et al, 2021 ; Tammam et al, 2021 ; Zhou, Krishnan, Jiang, Fang, & Zhang, 2021 ).…”

“…Lipid nanoparticles have been developed as the carrier of mRNA-based vaccine, which encodes for a full length, prefusion stabilized S protein of SARS-CoV-2 ( Al-Hatamleh et al, 2021 ; Shah et al, 2021 ). Nanoformulation of remdesivir with PEGylated dendrimer is translated to sustained drug release behaviour and reduced frequent drug dosing ( Tammam et al, 2021 ). Nanoformulation of dexamethasone, administered via injection or inhalation, has been developed to improve anti-COVID-19 treatment efficacy ( Lammers et al, 2020 ).…”

Viral and Host Genetic and Epigenetic Biomarkers Related to SARS-CoV-2 Cell Entry, Infection Rate, and Disease Severity

“…COVID-19 symptoms are fever, a dry cough, dyspnoea, myalgia, and pneumonia. Some patients also reported sore throat, rhinorrhoea, headache, and hyposmia [ 12 ]. COVID-19 patients that needed hospitalization or intensive care unit (ICU) presented with pneumonia with fever, lymphopenia, highly elevated pro-inflammatory cytokines, C-reactive protein (CRP), serum ferritin, and D-dimers [ 13 ].…”