Cell culture models of the respiratory tract relevant to pulmonary drug delivery.
The respiratory tract holds promise as an alternative site of drug delivery due to fast absorption and rapid onset of drug action, with avoidance of hepatic and intestinal first-pass metabolism as an additional benefit compared to oral drug delivery. At present, the pharmaceutical industry increasingly relies on appropriate in vitro models for the faster evaluation of drug absorption and metabolism as an alternative to animal testing. This article reviews the various existing cell culture systems that may be applied as in vitro models of the human air-blood barrier, for instance, in order to enable the screening of large numbers of new drug candidates at low cost with high reliability and within a short time span. Apart from such screening, cell culture-based in vitro systems may also contribute to improve our understanding of the mechanisms of drug transport across such epithelial tissues, and the mechanisms of action how advanced drug carriers, such as nanoparticles or liposomes, can help to overcome these barriers. After all, the increasing use and acceptance of such in vitro models may lead to a significant acceleration of the drug development process by facilitating the progress into clinical studies and product registration.
Steimer
A
A
Across Barriers GmbH, Department R&D Cell & Tissue Based Systems, Science Park Saar, Saarbrücken, Germany.
Haltner
E
E
Lehr
C-M
CM
D000826:Animal Testing Alternatives; D001980:Bronchi / Q000166:cytology; D018938:Caco-2 Cells; D022461:Caveolins / Q000378:metabolism; D018929:Cell Culture Techniques; D002463:Cell Membrane Permeability; D002478:Cells, Cultured; D004848:Epithelium / Q000378:metabolism; D006801:Humans; D017136:Ion Transport; D008954:Models, Biological; D004364:Pharmaceutical Preparations / Q000008:administration & dosage*; D011650:Pulmonary Alveoli / Q000166:cytology / Q000378:metabolism; D012137:Respiratory System / Q000378:metabolism*
D022461:Caveolins; D004364:Pharmaceutical Preparations