University of Hertfordshire

From the same journal

By the same authors

  • Victoria Hutter
  • Constanze Hilgendorf
  • Anne Cooper
  • Vanessa Zann
  • David Pritchard
  • Cynthia Bosquillon
View graph of relations
Original languageEnglish
Pages (from-to)481-489
Number of pages9
JournalEuropean Journal of Pharmaceutical Sciences
Volume47
Issue2
Early online date20 Jul 2012
DOIs
Publication statusPublished - 29 Sep 2012

Abstract

A rat respiratory epithelial cell culture system for in vitro prediction of drug pulmonary absorption is currently lacking. Such a model may however enhance the understanding of interspecies differences in inhaled drug pharmacokinetics by filling the gap between human in vitro and rat in/ex vivo drug permeability screens. The rat airway epithelial cell line RL-65 was cultured on Transwell® inserts for up to 21days at an air-liquid (AL) interface and cell layers were evaluated for their suitability as a drug permeability measurement tool. These layers were found to be morphologically representative of the bronchial/bronchiolar epithelium when cultured for 8days in a defined serum-free medium. In addition, RL-65 layers developed epithelial barrier properties with a transepithelial electrical resistance (TEER) >300Ωcm(2) and apparent (14)C-mannitol permeability (P(app)) values between 0.5-3.0×10(-6)cm/s; i.e., in the same range as established in vitro human bronchial epithelial absorption models. Expression of P-glycoprotein was confirmed by gene analysis and immunohistochemistry. Nevertheless, no vectorial transport of the established substrates (3)H-digoxin and Rhodamine123 was observed across the layers. Although preliminary, this study shows RL-65 cell layers have the potential to become a useful in vitro screening tool in the pre-clinical development of inhaled drug candidates.

ID: 988141