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- W57376447 abstract "Objective Paracellular pathway is a principal route for absorption of biologics (peptides, proteins and nucleic acids); however, tight junctions (TJs) restrict passing of biologics across epithelium. Claudin is known as a key component in TJs-barrier. We previously found that a claudin-4 modulator, C-terminal fragment of Clostridium perfringens enterotoxin (C-CPE), enhanced jejunal absorption of dextran. In this study, we investigated whether a claudin-4 modulator is a potent mucosal absorption-enhancer of a peptide drug. Methods Mucosal absorption was evaluated by rat jejunal, pulmonary and nasal administration of human parathyroid hormone derivative, hPTH(1–34) and C-CPEs. Plasma hPTH(1–34) levels were measured by RIA. Binding of C-CPEs to claudin-4 was assayed by ELISA and BIAcore analysis. Results Pre-treatment with C-CPE enhanced mucosal absorption of hPTH(1–34). However, the jejunal and pulmonary absorption-enhancing effects were not observed by co-treatment with C-CPE. The deletion of 10 amino acids at the N-terminal of C-CPE increased its solubility by 30-fold. Moreover, the truncated C-CPE bound to claudin-4, modulated the TJ-barrier and enhanced jejunal absorption of dextran. Co-treatment of the truncated C-CPE also enhanced jejunal and pulmonary absorption of hPTH(1–34). Conclusion Claudin-4 modulator may be a promising absorption-enhancer of a peptide drug." @default.
- W57376447 created "2016-06-24" @default.
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- W57376447 date "2010-04-01" @default.
- W57376447 modified "2023-10-01" @default.
- W57376447 title "A claudin‐4 modulator enhances the mucosal absorption of peptide" @default.
- W57376447 doi "https://doi.org/10.1096/fasebj.24.1_supplement.lb648" @default.
- W57376447 hasPublicationYear "2010" @default.
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