COVID-19 - Coronavirus disease 2019

Nanoformulations of current therapeutic drug candidates against SARS-CoV-2 for pulmonary delivery – CovidNanoMed

Submission summary

Therapeutic options in response to the SARS-Cov-2 outbreak are urgently needed and existing one are still limited. Facing pandemic development, actual strategy has been to repurpose some existing antiviral drugs used against respiratory diseases (SARS-Cov-1, MERS, Influenza) or chronic diseases (HIV-1, HCV, HBV, etc…). However, side effects are common and required short treatment mainly through intravenous injection, with a non optimal dose, and rarely through pulmonary route. A better formulation of such drug, adapted to this pulmonary disease, will allow an optimal efficacy of current drug or new candidates, such as protease inhibitors. Nanomedicine tools, such as used in HIV-1 treatment, could provide some solution by proposing innovative formulation, leading to the same efficacy with low dose of drugs and nasal/pulmonary delivery. Furthermore, nanoparticulate form favors drug stability, when present in aerosol via sprays or nebulizers. Thus, the CoviNanoMed project aims to formulate and test potential antiviral drugs or Host Targeted Agents using an existing robust nanoparticle platform in order to increase their potential efficacy, while diminishing their side effects. To this aim, we have identified six promising candidates, (non-exhaustive list which could be modulated according to ongoing clinical trials) and have gather four complementary research groups to: i) select the most promising for nanoformulation through in silico modeling and prepare reproducible and stable batch of nanodrugs ii) Assess their antiviral activities and toxicities using state of the art technique, adapted to their nanoparticulate form. It will allow us to classify them and to integrate in an iterative manner new ones according to collaborators iii) Compare nasal and pulmonary delivery in mice through devices used in clinical setting. We will use fluorescent particles and whole body imagine in mice and Non Human Primates to analyze the fate of particles in lung cells and tissue, and iv) Analyse drug release in bronchoalveolar fluids in mice and the most promising formulations in Non Human Primate. As this project concerns existing drugs, the analytical protocols and methods are already determined and will be quickly available.
By this project, we expect to identify at least one promising candidate that could be quickly moved to clinical trial, as the biodegradable platform we propose will be considered as a new formulating excipient. Our system is solely based on poly–lactic acid (PLA), a biodegradable polymer approved by the FDA for medical devices such as sutures. It is therefore free of any controversial surfactant that frequently prevent the development of nanosystems to late phases. Additionally, the methodology we have set up could be adapted to new compounds that will emerge through ongoing clinical trials such as the multiple protease inhibitors that are undergoing studies.

Project coordination

Bernard VERRIER (BIOLOGIE TISSULAIRE ET INGENIERIE THERAPEUTIQUE)

The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.

Partner

LBTI BIOLOGIE TISSULAIRE ET INGENIERIE THERAPEUTIQUE
IDMIT Département lnfectious Disease Models and lnnovative Therapies
IVPC Infections virales et Pathologie Comparée

Help of the ANR 198,067 euros
Beginning and duration of the scientific project: April 2020 - 18 Months

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