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dc.contributor.authorHutter, Victoria
dc.contributor.authorHilgendorf, Constanze
dc.contributor.authorCooper, Anne
dc.contributor.authorZann, Vanessa
dc.contributor.authorPritchard, David
dc.contributor.authorBosquillon, Cynthia
dc.identifier.citationHutter , V , Hilgendorf , C , Cooper , A , Zann , V , Pritchard , D & Bosquillon , C 2012 , ' Evaluation of layers of the rat airway epithelial cell line RL-65 for permeability screening of inhaled drug candidates. ' , European Journal of Pharmaceutical Sciences , vol. 47 , no. 2 , pp. 481-489 .
dc.identifier.otherPURE: 988141
dc.identifier.otherPURE UUID: 756cbc0a-c032-4cf0-9df6-7e95627fd6c5
dc.identifier.otherScopus: 84864496479
dc.description.abstractA 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.en
dc.relation.ispartofEuropean Journal of Pharmaceutical Sciences
dc.titleEvaluation of layers of the rat airway epithelial cell line RL-65 for permeability screening of inhaled drug candidates.en
dc.contributor.institutionDepartment of Pharmacy
dc.contributor.institutionHealth & Human Sciences Research Institute
dc.contributor.institutionCentre for Research into Topical Drug Delivery and Toxicology
dc.contributor.institutionAirway Group
dc.description.statusPeer reviewed
rioxxterms.typeJournal Article/Review

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