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- W2897095887 abstract "As a unique macromolecular permeation enhancer, thiolated polymers (thiomers), especially the preactivated thiomers, have demonstrated great merits in oral delivery of protein/peptide drugs by triggering epithelial tight junctions (TJs) opening. However, the underlying molecular mechanism remains unclear. To clarify this issue, preactivated thiomers were synthesized and their TJs opening function as well as signaling pathways on MDCK and Caco-2 cell monolayers was investigated. The results showed that preactivated thiomers could reduce TEER and increase the permeation of Na-Flu and FITC-Insulin over 2-fold and 4-fold on MDCK monolayers, respectively, indicating their huge potential as macromolecular permeation enhancers. The signaling pathway study showed that intracellular PTK Src but not FAK, involved in the TJs opening by claudin-4 disruption. Src activation was based on interaction between thiol group of thiomers and cysteine-riched Src upstream membrane receptors, EGFR and IGFR. The deep comprehension of the thiomers-mediated TJs opening mechanisms provides goodness in application of protein/peptide drugs for the oral delivery." @default.
- W2897095887 created "2018-10-26" @default.
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- W2897095887 date "2018-12-01" @default.
- W2897095887 modified "2023-10-15" @default.
- W2897095887 title "The function and mechanism of preactivated thiomers in triggering epithelial tight junctions opening" @default.
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- W2897095887 doi "https://doi.org/10.1016/j.ejpb.2018.10.014" @default.
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