Comparison of human tracheal/bronchial epithelial cell culture and bovine nasal respiratory explants for nasal drug transport studies.
Ten drug compounds with varying physicochemical properties and transporter substrate specificities were investigated to compare their in vitro permeabilities across bovine nasal respiratory explants and the EpiAirway system, both established models for the assessment of nasal drug absorption. Permeability across the bovine explants and EpiAirway correlated well with the partitioning behavior of compounds whose clogDC values were greater than 0. The permeabilities of all ten compounds were well-correlated between the two tissue models, with the permeability values through the EpiAirway tissues being approximately 10-fold higher than through the bovine explants due to the thickness differences between the models. For more lipophilic compounds, the in vitro permeabilities measured with both tissue systems were also predictive of the reported in vivo nasal bioavailabilities. Deviations from these correlations were observed for compounds reported to be substrates of p-glycoprotein or OCT transporters, and differences were also seen between the permeabilities measured in the tissue models for these compounds. Both models can be used to estimate the systemic bioavailability of moderately lipophilic compounds administered intranasally, while each may have particular advantages or disadvantages in estimating the bioavailability of drug compounds that are subject to local mucosal metabolism or to carrier-mediated uptake or efflux.
Chemuturi
Nagendra V
NV
Division of Pharmaceutics, College of Pharmacy, University of Iowa, Iowa City, Iowa 52242, USA.
Hayden
Patrick
P
Klausner
Mitch
M
Donovan
Maureen D
MD
D000818:Animals; D001692:Biological Transport; D001980:Bronchi / Q000378:metabolism; D002417:Cattle; D002463:Cell Membrane Permeability; D002478:Cells, Cultured; D015194:Diffusion Chambers, Culture; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism* / Q000648:ultrastructure; D006801:Humans; D046529:Microscopy, Electron, Transmission; D009297:Nasal Mucosa / Q000378:metabolism*; D004364:Pharmaceutical Preparations / Q000737:chemistry / Q000378:metabolism*; D015203:Reproducibility of Results; D020545:Respiratory Mucosa / Q000166:cytology / Q000378:metabolism* / Q000648:ultrastructure; D014132:Trachea / Q000378:metabolism
D004364:Pharmaceutical Preparations