Large porous particle impingement on lung epithelial cell monolayers - Toward improved particle characterization in the lung

Jennifer Fiegel, Carsten Ehrhardt, Ulrich Friedrich Schaefer, Claus Michael Lehr, Justin Hanes

Research output: Contribution to journalArticlepeer-review

Abstract

Purpose. The ability to optimize new formulations for pulmonary delivery has been limited by inadequate in vitro models used to mimic conditions particles encounter in the lungs. The aim is to develop a physiologically-relevant model of the pulmonary epithelial barrier that would allow for quantitative characterization of therapeutic aerosols in vitro. Methods. Calu-3 human bronchial epithelial cells were cultured on permeable filter inserts under air-interfaced culture (AIC) and liquid-covered culture (LCC) conditions. Calu-3 ceils grown under both conditions formed tight monolayers and appeared physiologically similar by SEM and immunocytochemical staining against cell junctional proteins and prosurfactant protein-C. Results. Aerosolized large porous particles (LPP) deposited homogeneously and reproducibly on the cell surface and caused no apparent damage to cell monolayers by SEM and light microscopy. However, monolayers initially grown under LCC conditions showed a significant decrease in barrier properties within the first 90 min after impingement with microparticles, as determined by transepithelial electrical resistance (TEER) measurements and fluorescein-sodium transport. Conversely, AIC grown monolayers showed no significant change in barrier properties within the first 90 rain following particle application. A dense mucus coating was found on AIC grown Calu-3 monolayers, but not on LCC grown monolayers, which may protect the cell surface during particle impinging. Conclusions. This in vitro model, based on AIC grown Calu-3 cells, should allow a more relevant and quantitative characterization of therapeutic aerosol particles intended for delivery to the tracheobronchial region of the lung or to the nasal passages. Such characterization is likely to be particularly important with therapeutic aerosol particles designed to provide sustained drug release in the lung.

Original languageEnglish (US)
Pages (from-to)788-796
Number of pages9
JournalPharmaceutical Research
Volume20
Issue number5
DOIs
StatePublished - May 1 2003

Keywords

  • Calu-3
  • In vitro model
  • Microparticles
  • Pulmonary drug delivery

ASJC Scopus subject areas

  • Biotechnology
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry
  • Pharmacology (medical)

Fingerprint Dive into the research topics of 'Large porous particle impingement on lung epithelial cell monolayers - Toward improved particle characterization in the lung'. Together they form a unique fingerprint.

Cite this