Permeability Characteristics of calu-3 Human Bronchial Epithelial Cells: In Vitro-In Vivo Correlation to Predict Lung Absorption in Rats

J Drug Target. 2002 Feb;10(1):31-40. doi: 10.1080/10611860290007504.

Abstract

The goal of this study was to evaluate the permeability characteristics of Calu-3, human bronchial epithelial cells to passive and actively transported drugs and to correlate the data with other in vitro models and rat lung absorption in vivo. Air-interface cultured Calu-3 cells grown on collagen-coated permeable filter supports formed "tight" polarized and well differentiated cell monolayers with apical microvilli and tight-junctional complexes. Within 8-10 days, cell monolayers developed trans-epithelial electrical resistance (TEER) > 1000 ohm cm2 and potential difference about 11-16 mV. Solute permeability was dependent on lipophilicity, and inversely related to molecular size. Calu-3 cells actively transported amino acids, nucleosides and dipeptide analogs, but not organic anions, organic cations or efflux pump substrates. The permeability characteristics of Calu-3 cells correlated well with primary cultured rabbit tracheal epithelial cells in vitro (r2 = 0.91), and the rate of drug absorption from the rat lung in vivo (r2 = 0.94). The absorption predicted from the regression equation correlated well with observed values. In conclusion, in vitro-in vivo correlation studies indicate that the Calu-3 cell culture model is a potentially useful model to predict absorption of inhalation delivery drug candidates.

MeSH terms

  • Absorption
  • Administration, Inhalation
  • Algorithms
  • Animals
  • Biological Transport
  • Bronchi / cytology*
  • Bronchi / physiology
  • Bronchi / ultrastructure
  • Cell Line
  • Cell Membrane Permeability / physiology*
  • Cells, Cultured
  • Chemical Phenomena
  • Chemistry, Physical
  • Epithelial Cells / physiology*
  • Epithelial Cells / ultrastructure
  • Half-Life
  • Humans
  • Lung / metabolism*
  • Microscopy, Electron
  • Patch-Clamp Techniques
  • Pharmaceutical Preparations / chemistry
  • Pharmaceutical Preparations / metabolism
  • Rats

Substances

  • Pharmaceutical Preparations