Assessment of transport rates of proteins and peptides across primary human alveolar epithelial cell monolayers

European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences
Michael BurCarsten Ehrhardt

Abstract

In this study, we investigated bi-directional fluxes (i.e., in absorptive and secretive directions) of human serum proteins [albumin (HSA), transferrin (TF), and immunoglobulin G (IgG)] and peptides/proteins of potential therapeutic relevance [insulin (INS), glucagon-like peptide-1 (GLP-1), growth hormone (GH), and parathyroid hormone (PTH)] across tight monolayers of human alveolar epithelial cells (hAEpC) in primary culture. Apparent permeability coefficients (P(app); x10(-7)cm/s, mean+/-S.D.) for GLP-1 (6.13+/-0.87 (absorptive) versus 1.91+/-0.51 (secretive)), HSA (2.45+/-1.02 versus 0.21+/-0.31), TF (0.88+/-0.15 versus 0.30+/-0.03), and IgG (0.36+/-0.22 versus 0.15+/-0.16) were all strongly direction-dependent, i.e., net absorptive, while PTH (2.20+/-0.30 versus 1.80+/-0.77), GH (8.33+/-1.24 versus 9.02+/-3.43), and INS (0.77+/-0.15 versus 0.72+/-0.36) showed no directionality. Trichloroacetic acid precipitation analysis of tested molecules collected from donor and receiver fluids exhibited very little degradation. This is the first study on permeability data for a range of peptides and proteins across an in vitro model of the human alveolar epithelial barrier. These data indicate that there is no apparent size-dependent tr...Continue Reading

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Citations

Feb 21, 2009·Molecular Pharmaceutics·Leena N PatelWei-Chiang Shen
Oct 6, 2009·Biological & Pharmaceutical Bulletin·Mika IkehataMikihisa Takano
Aug 8, 2013·Therapeutic Delivery·Mariam Ibrahim, Lucila Garcia-Contreras
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Jun 2, 2018·Alternatives to Laboratory Animals : ATLA·Sandra SapichClaus-Michael Lehr
Jan 30, 2021·Alternatives to Laboratory Animals : ATLA·Julia Katharina MetzMarius Hittinger

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