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• W1982823547 abstract "The apparent permeability coefficient (Papp) of two fluorescently tagged model hydrophilic peptides, acXASNH2 and acXAS(GAS)7NH2, and 14C‐mannitol across monolayers of cultured rat alveolar epithelial cells of varying transepithelial electrical resistance (TER) has been examined. In line with their design features, the peptides were not degraded under the conditions of the test. Furthermore, no concentration dependence of transport of the tripeptide acXASNH2 was observed over the concentration range studied, nor was any directional transport seen for either of the model peptides, indicating that under the conditions of the test they were not substrates for any transporters or efflux pumps. From the hydrophilic nature of the peptides (as assessed by their log P), and their inverse dependence of transport with molecular weight and TER, it was assumed that the peptides were transported across the cell monolayer passively via the paracellular route. The observed Papp for the transport of 14C‐mannitol and the peptides across rat alveolar epithelial cell monolayers were found to be inversely (though not linearly) related to the measured TER and could be well‐modeled assuming the presence of two populations of “pores” in the cell monolayer, namely, cylindrical pores of diameter 1.5 nm and large pores of diameter 20 nm. The relative populations of the two types of pores varied with the TER of the monolayer, with the number of large pores decreasing with an increase in TER (and the number of small pores taken as fixed). These results suggest that if the cell monolayer is well characterized with respect to the passage of a range of probe molecules across monolayers of varying electrical resistance, it should be possible to predict the Papp of any hydrophilic peptide or drug crossing the membrane by the paracellular route at any desired TER using a monolayer of any electrical resistance, above a minimum value. © 2000 Wiley‐Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 89: 223–231, 2000" @default.
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• W1982823547 date "2000-02-01" @default.
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• W1982823547 title "Use of Alveolar Cell Monolayers of Varying Electrical Resistance to Measure Pulmonary Peptide Transport" @default.
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• W1982823547 doi "https://doi.org/10.1002/(sici)1520-6017(200002)89:2<223::aid-jps9>3.0.co;2-r" @default.
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