Journal article
Large porous particle impingement on lung epithelial cell monolayers--toward improved particle characterization in the lung
Pharmaceutical research, Vol.20(5), pp.788-796
05/2003
DOI: 10.1023/A:1023441804464
PMID: 12751635
Abstract
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.
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 cells grown under both conditions formed tight monolayers and appeared physiologically similar by SEM and immunocytochemical staining against cell junctional proteins and prosurfactant protein-C.
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 min 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.
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.
Details
- Title: Subtitle
- Large porous particle impingement on lung epithelial cell monolayers--toward improved particle characterization in the lung
- Creators
- Jennifer Fiegel - Johns Hopkins UniversityCarsten Ehrhardt - Saarland UniversityUlrich Friedrich Schaefer - Saarland UniversityClaus-Michael LehrJustin Hanes - Johns Hopkins University School of Medicine
- Resource Type
- Journal article
- Publication Details
- Pharmaceutical research, Vol.20(5), pp.788-796
- DOI
- 10.1023/A:1023441804464
- PMID
- 12751635
- ISSN
- 0724-8741
- eISSN
- 1573-904X
- Language
- English
- Date published
- 05/2003
- Academic Unit
- Pharmaceutical Sciences and Experimental Therapeutics; Chemical and Biochemical Engineering
- Record Identifier
- 9984197096302771
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