{
    "abstract": "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\u202fh 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": [
        {
            "affiliation": "Universit\u00e9 Paris-Saclay, CNRS, Institut des Sciences Mol\u00e9culaires d'Orsay 91405 Orsay, France.",
            "firstname": "Tom",
            "initials": "T",
            "lastname": "Bourguignon"
        },
        {
            "affiliation": "Universit\u00e9 Paris-Saclay, CNRS, Institut des Sciences Mol\u00e9culaires d'Orsay 91405 Orsay, France.",
            "firstname": "Jesus Alfredo",
            "initials": "JA",
            "lastname": "Godinez-Leon"
        },
        {
            "affiliation": "Universit\u00e9 de Lille, CNRS, INSERM, CHU de Lille, Institut Pasteur de Lille, U1019 - UMR 9017 - CIIL - Center for Infection and Immunity of Lille F-59000 Lille, France.",
            "firstname": "Amine",
            "initials": "A",
            "lastname": "Pochet"
        },
        {
            "affiliation": "Universit\u00e9 Paris-Saclay, CNRS, Institut des Sciences Mol\u00e9culaires d'Orsay 91405 Orsay, France.",
            "firstname": "Tahmida",
            "initials": "T",
            "lastname": "Shamsuddin"
        },
        {
            "affiliation": "Universit\u00e9 de Lille, CNRS, INSERM, CHU de Lille, Institut Pasteur de Lille, U1019 - UMR 9017 - CIIL - Center for Infection and Immunity of Lille F-59000 Lille, France.",
            "firstname": "Valentin",
            "initials": "V",
            "lastname": "Sencio"
        },
        {
            "affiliation": "Universit\u00e9 de Lille, CNRS, INSERM, CHU de Lille, Institut Pasteur de Lille, U1019 - UMR 9017 - CIIL - Center for Infection and Immunity of Lille F-59000 Lille, France.",
            "firstname": "Jonathan",
            "initials": "J",
            "lastname": "Chatagnon"
        },
        {
            "affiliation": "Universit\u00e9 de Lille, CNRS, INSERM, CHU de Lille, Institut Pasteur de Lille, U1019 - UMR 9017 - CIIL - Center for Infection and Immunity of Lille F-59000 Lille, France.",
            "firstname": "Axelle",
            "initials": "A",
            "lastname": "Grand\u00e9"
        },
        {
            "affiliation": "Universit\u00e9 de Lille, CNRS, INSERM, CHU de Lille, Institut Pasteur de Lille, U1019 - UMR 9017 - CIIL - Center for Infection and Immunity of Lille F-59000 Lille, France.",
            "firstname": "Joan",
            "initials": "J",
            "lastname": "Fine"
        },
        {
            "affiliation": "Universit\u00e9 de Lille, CNRS, INSERM, CHU de Lille, Institut Pasteur de Lille, U1019 - UMR 9017 - CIIL - Center for Infection and Immunity of Lille F-59000 Lille, France.",
            "firstname": "S\u00e9verine",
            "initials": "S",
            "lastname": "Heumel"
        },
        {
            "affiliation": "Universit\u00e9 de Lille, CNRS, INSERM, CHU de Lille, Institut Pasteur de Lille, U1019 - UMR 9017 - CIIL - Center for Infection and Immunity of Lille F-59000 Lille, France.",
            "firstname": "Cyril",
            "initials": "C",
            "lastname": "Robil"
        },
        {
            "affiliation": "Universit\u00e9 de Lille, CNRS, INSERM, CHU de Lille, Institut Pasteur de Lille, U1019 - UMR 9017 - CIIL - Center for Infection and Immunity of Lille F-59000 Lille, France.",
            "firstname": "Lou",
            "initials": "L",
            "lastname": "Delval"
        },
        {
            "affiliation": "Inserm, Institut Pasteur de Lille, U1177-Drugs and Molecules for Living Systems, University of Lille, Lille, France.",
            "firstname": "Catherine",
            "initials": "C",
            "lastname": "Piveteau"
        },
        {
            "affiliation": "Universit\u00e9 de Lille, CNRS, INSERM, CHU de Lille, Institut Pasteur de Lille, U1019 - UMR 9017 - CIIL - Center for Infection and Immunity of Lille F-59000 Lille, France.",
            "firstname": "Sandrine",
            "initials": "S",
            "lastname": "Belouzard"
        },
        {
            "affiliation": "Universit\u00e9 de Lille, CNRS, INSERM, CHU de Lille, Institut Pasteur de Lille, U1019 - UMR 9017 - CIIL - Center for Infection and Immunity of Lille F-59000 Lille, France.",
            "firstname": "Priscille",
            "initials": "P",
            "lastname": "Brodin"
        },
        {
            "affiliation": "Universit\u00e9 de Lille, CNRS, INSERM, CHU de Lille, Institut Pasteur de Lille, U1019 - UMR 9017 - CIIL - Center for Infection and Immunity of Lille F-59000 Lille, France.",
            "firstname": "Fran\u00e7ois",
            "initials": "F",
            "lastname": "Trottein"
        },
        {
            "affiliation": "Universit\u00e9 de Lille, CNRS, INSERM, CHU de Lille, Institut Pasteur de Lille, U1019 - UMR 9017 - CIIL - Center for Infection and Immunity of Lille F-59000 Lille, France. Electronic address: arnaud.machelart@inserm.fr.",
            "firstname": "Arnaud",
            "initials": "A",
            "lastname": "Machelart"
        },
        {
            "affiliation": "Universit\u00e9 Paris-Saclay, CNRS, Institut des Sciences Mol\u00e9culaires d'Orsay 91405 Orsay, France. Electronic address: ruxandra.gref@cnrs.fr.",
            "firstname": "Ruxandra",
            "initials": "R",
            "lastname": "Gref"
        }
    ],
    "conclusions": null,
    "copyrights": "Copyright \u00a9 2025 The Author(s). Published by Elsevier B.V. All rights reserved.",
    "doi": "10.1016/j.ijpharm.2025.125634",
    "journal": "International journal of pharmaceutics",
    "keywords": [
        "COVID-19",
        "Clofoctol",
        "Lung infection",
        "Lung inflammation",
        "Nanomedicine",
        "PLGA nanoparticles"
    ],
    "methods": null,
    "publication_date": "2025-04-26",
    "pubmed_id": "40280285",
    "results": null,
    "title": "Pulmonary delivery of clofoctol-loaded nanoparticles inhibits SARS-CoV-2 replication and reduces pneumonia.",
    "xml": "<Element 'PubmedArticle' at 0x788503bfea70>"
}