Pulmonary delivery of clofoctol-loaded nanoparticles inhibits SARS-CoV-2 replication and reduces pneumonia
Despite the progress made through vaccination campaigns and the use of antivirals, the need for more effective therapeutics to combat respiratory viral infections remains critical. A recent screening of over 2000 repurposed molecules has identified the antibiotic clofoctol (CFT) as a promising candidate for treating COVID-19. However, administering CFT systemically poses challenges due to its low solubility and potential toxicity. In this study, we engineered poly(lactic-co-glycolic) acid (PLGA)-based nanoparticles (NPs) designed to encapsulate high payloads of CFT, allowing for a controlled drug release in the pulmonary environment. Pharmacokinetic studies demonstrated high CFT bioavailability 8 h after intranasal (i.n.) administration. In preclinical models (mouse and hamster) of COVID-19, i.n. administration of CFT-loaded NPs significantly reduced pulmonary viral loads. Remarkably, vectorized CFT also decreased inflammation and improved pathological scores in the lungs. These results pave the way for a groundbreaking CFT formulation designed to tackle the challenges posed by acute respiratory infections. This study marks the first demonstration of a stable, effective and well-tolerated CFT formulation for the treatment of lung diseases.
Authors
- Jesus Alfredo Godinez-Leon (ORCID: https://orcid.org/0000-0001-9498-4693)
- Cyril Robil (ORCID: https://orcid.org/0000-0002-3607-244X)
- Arnaud Machelart (ORCID: https://orcid.org/0000-0002-4444-0011)
- Ruxandra Gref (ORCID: https://orcid.org/0000-0002-7869-0908)
- Janelle M. Fine (ORCID: https://orcid.org/0000-0002-6800-4222)
- Séverine Heumel (ORCID: https://orcid.org/0000-0001-8649-5814)
- Sandrine Belouzard (ORCID: https://orcid.org/0000-0002-9972-4054)
- Lou Delval (ORCID: https://orcid.org/0000-0002-3854-4439)
- François Trottein (ORCID: https://orcid.org/0000-0003-3373-1814)
- Amine Pochet (ORCID: https://orcid.org/0009-0003-5900-0769)
- Tom Bourguignon (ORCID: https://orcid.org/0000-0001-5356-4000)
- Valentin Sencio (ORCID: https://orcid.org/0000-0002-6379-4317)
- Jonathan Chatagnon (ORCID: https://orcid.org/0000-0003-0496-8548)
- Catherine Piveteau (ORCID: https://orcid.org/0000-0002-3835-4619)
- Priscille Brodin (ORCID: https://orcid.org/0000-0003-0991-7344)
- Tahmida Shamsuddin
Institutions
- Centre National de la Recherche Scientifique (FR)
- Inserm (FR)
- Université Paris-Saclay (FR)
- Institut Pasteur de Lille (FR)
- Centre Hospitalier Universitaire de Lille (FR)
- Center for Infection and Immunity of Lille (FR)
- Institut des Sciences Moléculaires d'Orsay (FR)
Publication Details
- Journal
- International Journal of Pharmaceutics
- Published
- 2025-04-23
- DOI
- https://doi.org/10.1016/j.ijpharm.2025.125634
- Citations
- 2
- Primary Topic
- Inhalation and Respiratory Drug Delivery
- Type
- article
- Field-Weighted Citation Impact
- 3.04