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

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.

Liposomal delivery of functional transmembrane ion channels into the cell membranes of target cells; a potential approach for the treatment of channelopathies.

Defects in transmembrane ion channels underlie many disorders, commonly known as channelopathies. Current therapies are mostly symptomatic and do not treat the underlying cause. Here, we demonstrate the delivery of functional ion channels in protein form into the membrane of target cells using fusogenic proteoliposomes. The glycine receptor (GlyR) was adopted as a model channel. HEK293 cells were transfected with GlyR and GlyR-rich cell membrane fragments (CMF) were incorporated into fusogenic liposomes. Proteoliposomes were generated using 1,2-dioleoylphosphoethanolamine (DOPE) as the fusogenic lipid, lecithin, 1,2-distearoylphosphoethanolamine (DSPE), and cholesterol (Chol). Three formulations were prepared Non-fuse (2.5:0.5 Lecithin: Chol), Fuse1 (1.25:0.25:0.25:0.25) and Fuse2 (1.25:0.5:0.5:0.25 Lecithin: DOPE: DSPE: Chol). Proteoliposomes were assessed for their ability to (1) incorporate GlyR rich CMF (2) fuse with L929 fibroblast cell membrane and (3) deliver functional GlyR to these cells. All formulations were capable of integrating CMF, with Fuse2 showing highest CMF incorporation (1.2 and 1.4 folds relative to Non-fuse and Fuse1 respectively). All liposomes showed ability to fuse with the fibroblast cell membrane, with Fuse2 showing highest fusion. Patch-clamp analysis demonstrated successful delivery of functional GlyR into the fibroblast cell membrane. Thus, proof of principle was established for the use of liposomes to deliver functional ion channels to living cells.