{
  "abstract": "Unlike traditional submerged cell cultures, nebulized drug delivery to air-liquid interface (ALI)-cultured lung cells provides a clinically relevant route for in vitro testing of inhalable drugs. Current nebulizer systems deliver non-physiologically large drug volumes. Here, we introduce the Cloud MAX technology, characterize its accuracy of dosimetry, and apply it to toxicity, efficacy, and biokinetics or permeability testing of a locked nucleic acid-modified antisense oligonucleotide (ASO). On average the Cloud MAX delivers 44% of 3-20 μL aerosolized liquid to ALI-cultured cells, the coefficient of variation (CV) of repeated drug dosing is <11%-rel. and as little as 1 μL of drug/insert (=0.25 μL/cm2) can be delivered to ALI-cultured cells. As proof of concept for dose-controlled in vitro drug testing, we demonstrated target engagement of a LIM and Calponin Homology domain 1 (LIMCH1)-specific ASO in primary lung fibroblasts from Idiopathic Pulmonary Fibrosis (IPF) patients \"shielded\" by an A549 alveolar epithelial layer mimicking inhalation therapy. LIMCH1-ASO was effective in LIMCH1-silencing even at the lowest dose (0.64 nmol/cm2). Nebulization did neither impair LIMCH1-ASO efficacy nor induce cytotoxicity for the highest tested dose (3.21 nmol/cm2). The permeability (biokinetics) of nebulized ASO through the A549 cell barrier was 14-fold faster (\"burst-like\") than for larger volume (pipetted) ASO application. Computational modeling revealed that this well-known \"burst-like\" pharmaco-/biokinetics profile is due to small-volume drug application, not due to nebulizer-induced changes on barrier tightness (apparent permeability Papp ). Thus, the Cloud MAX is a substance-efficient platform for in vitro pharmacokinetics/-dynamics testing of inhalable drugs for targeted pulmonary therapy.",
  "abstract_shown": true,
  "affiliations": [
    "Institute of Lung Health and Immunity, Comprehensive Pneumology Center (CPC-M) with the CPC-M bioArchive, Ludwig-Maximilians-Universität München and Helmholtz Munich, Member of the German Center for Lung Research (DZL), Germany.",
    "Centre d'Etudes des Pathologies Respiratoires / Inserm UMR1100, Tours, France.",
    "Université de Tours, Tours, France.",
    "Secarna Pharmaceuticals GmbH & Co. KG, Planegg, Germany.",
    "Université catholique de Louvain, Louvain Drug Research Institute, Advanced Drug Delivery & Biomaterials, Belgium.",
    "CHRU de Tours, Service de Pneumologie et Explorations Fonctionnelles Respiratoires, Tours, France."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 13,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Pramod Kumar"
    },
    {
      "affs": [
        0
      ],
      "name": "Ashesh Chakraborty"
    },
    {
      "affs": [
        0
      ],
      "name": "Elias Richter"
    },
    {
      "affs": [
        0
      ],
      "name": "Lin Yang"
    },
    {
      "affs": [
        0
      ],
      "name": "Andreas Schröppel"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Coralie Mergault"
    },
    {
      "affs": [
        3
      ],
      "name": "Larissa Rothkirch Née Knüppel"
    },
    {
      "affs": [
        3
      ],
      "name": "Frank Jaschinski"
    },
    {
      "affs": [
        0
      ],
      "name": "Marion Blayac"
    },
    {
      "affs": [
        4
      ],
      "name": "Rita Vanbever"
    },
    {
      "affs": [
        1,
        2,
        5
      ],
      "name": "Laurent Plantier"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Nathalie Heuzé-Vourch"
    },
    {
      "affs": [
        0
      ],
      "name": "Otmar Schmid"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/3g7sv1crv7gte.bib",
  "cited_by": 1,
  "doi": "10.1016/j.ijpx.2026.100588",
  "fulltext_url": "https://europepmc.org/articles/PMC13743522",
  "id": "3g7sv1crv7gte",
  "issns": [
    "2590-1567"
  ],
  "landing_url": "https://europepmc.org/article/MED/42999459",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2740|Inhalation and Respiratory Drug Delivery"
    ]
  ],
  "openalex": "W7166817764",
  "pdf_url": "https://europepmc.org/articles/PMC13743522?pdf=render",
  "pmcid": "PMC13743522",
  "pmid": "42999459",
  "published": "2026-07-01",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/3g7sv1crv7gte.ris",
  "sources": [
    {
      "first_seen": "2026-11-09T15:20:42Z",
      "native_id": "MED:42999459",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42999459"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2740|Inhalation and Respiratory Drug Delivery",
      "subfield": "general"
    }
  ],
  "title": "Microliter-scale in vitro aerosol-cell delivery of inhalable antisense oligonucleotide (ASO) induces \"burst-like\" pharmacokinetics.",
  "title_text": "Microliter-scale in vitro aerosol-cell delivery of inhalable antisense oligonucleotide (ASO) induces \"burst-like\" pharmacokinetics.",
  "type": "peer-reviewed",
  "updated_at": "2026-11-09T15:20:42Z",
  "url": "https://research.draconitic.com/paper/3g7sv1crv7gte",
  "venue": "International journal of pharmaceutics: X",
  "versions": []
}