Evidence map›Paper›PMID 40746730›Full record

ArticleFrontiers in pharmacology2025

Assessment of drug permeability using a small airway microphysiological system.

Robert M Geiger, Shekh M Rahman, Md Shadiqur Rashid Roni, Catherine Sullenberger, Sabyasachy Mistry, Katherine Shea, Isra Tariq, Omnia A Ismaiel, Murali K Matta, Paula L Hyland and 8 more

Abstract read
In one paragraph

Article in Frontiers in pharmacology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Review
  2. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

18 authors.

Robert M GeigerDivision of Applied Regulatory Science, Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, United States Food and Drug Administration, Silver Spring, MD, United States.
Shekh M RahmanDivision of Applied Regulatory Science, Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, United States Food and Drug Administration, Silver Spring, MD, United States.
Md Shadiqur Rashid RoniDivision of Applied Regulatory Science, Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, United States Food and Drug Administration, Silver Spring, MD, United States.
Catherine SullenbergerDivision of Applied Regulatory Science, Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, United States Food and Drug Administration, Silver Spring, MD, United States.
Sabyasachy MistryDivision of Applied Regulatory Science, Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, United States Food and Drug Administration, Silver Spring, MD, United States.
Katherine SheaDivision of Applied Regulatory Science, Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, United States Food and Drug Administration, Silver Spring, MD, United States.
Isra TariqDivision of Applied Regulatory Science, Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, United States Food and Drug Administration, Silver Spring, MD, United States.
Omnia A IsmaielDivision of Applied Regulatory Science, Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, United States Food and Drug Administration, Silver Spring, MD, United States.
Murali K MattaDivision of Applied Regulatory Science, Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, United States Food and Drug Administration, Silver Spring, MD, United States.
Paula L HylandDivision of Applied Regulatory Science, Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, United States Food and Drug Administration, Silver Spring, MD, United States.
Sasha BerdichevskiEmulate, Inc., Boston, MA, United States.
Alexandre J S RibeiroDivision of Applied Regulatory Science, Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, United States Food and Drug Administration, Silver Spring, MD, United States.
Ksenia BlinovaDivision of Applied Regulatory Science, Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, United States Food and Drug Administration, Silver Spring, MD, United States.
Wenlei JiangOffice of Research and Standards, Office of Generic Drugs, Center for Drug Evaluation and Research, United States Food and Drug Administration, Silver Spring, MD, United States.
Ross L WalengaOffice of Research and Standards, Office of Generic Drugs, Center for Drug Evaluation and Research, United States Food and Drug Administration, Silver Spring, MD, United States.
Bryan NewmanOffice of Research and Standards, Office of Generic Drugs, Center for Drug Evaluation and Research, United States Food and Drug Administration, Silver Spring, MD, United States.
Donna A VolpeDivision of Applied Regulatory Science, Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, United States Food and Drug Administration, Silver Spring, MD, United States.
Kevin A FordDivision of Applied Regulatory Science, Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, United States Food and Drug Administration, Silver Spring, MD, United States.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Background: There is a need to reliably predict the permeability of inhaled compounds during the development of new and generic drugs. A small airway microphysiological system (MPS) that can recapitulate the pulmonary air-liquid interface (ALI) with primary epithelial and vascular endothelial cell layers may provide a more physiologically relevant environment for measuring drug permeability than simpler two-dimensional Methodology: Primary human lung epithelial cells were seeded onto the top channel of the chip and cultured for 14 days at ALI to promote monolayer differentiation, followed by addition of endothelial cells into the bottom channel. Due to the non-specific binding properties of polydimethylsiloxane (PDMS), a drug absorption study was conducted to quantify non-specific binding to the material. Drug permeability was evaluated by passing each compound (10 µM) through the top channel and measuring the amount of drug that permeated into the bottom channel over the time course of 30, 60, 120, and 180 min. Results: Confocal micrographs demonstrated the presence of tight junctions along with basal, goblet, and ciliated cells in the top channel and attachment of endothelial cells in the bottom channel. Insignificant nonspecific binding to the MPS was observed with albuterol sulfate, formoterol fumarate, and olodaterol hydrochloride (HCl), while fluticasone furoate showed significant nonspecific binding as only 6%-44% of the drug was recovered at 30 and 120 min, respectively. As a result, fluticasone furoate was excluded from further analysis. Permeability studies estimated an apparent permeability (P Discussion: Taken together, the small airway MPS recapitulated relevant cell types and many morphological features in the lung. The apparent permeabilities measured indicated that albuterol sulfate and formoterol fumarate would be categorized as highly permeable, while olodaterol HCl would be categorized as a low permeable drug.

Indexed as

inhaled drugsmicrophysiological systempermeabilityregulatory sciencesmall airway

Identifiers

PMID40746730
PMCPMC12312011

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.