کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2482738 1556295 2006 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Assessment of transport rates of proteins and peptides across primary human alveolar epithelial cell monolayers
موضوعات مرتبط
علوم پزشکی و سلامت داروسازی، سم شناسی و علوم دارویی اکتشاف دارویی
پیش نمایش صفحه اول مقاله
Assessment of transport rates of proteins and peptides across primary human alveolar epithelial cell monolayers
چکیده انگلیسی

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 (Papp; ×10−7 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 transport conforming to passive restricted diffusion for the tested substances across human alveolar barrier, in part confirming net absorptive transcytosis. The obtained data differ significantly from previously published reports utilising monolayers from different species. It can be concluded that the use of homologous tissue should be preferred to avoid species differences.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: European Journal of Pharmaceutical Sciences - Volume 28, Issue 3, June 2006, Pages 196–203
نویسندگان
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