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A Potential Mechanism of a Cationic Cyclopeptide for Enhancing Insulin Delivery across Caco-2 Cell Monolayers

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Indexed by:期刊论文

Date of Publication:2013-10-01

Journal:BIOLOGICAL & PHARMACEUTICAL BULLETIN

Included Journals:SCIE、PubMed、Scopus

Volume:36

Issue:10

Page Number:1602-1607

ISSN No.:0918-6158

Key Words:insulin; cationic cyclopeptide; tight junction; endocytosis; paracellular delivery

Abstract:Effective delivery of therapeutic biomolecules across biomembranes is a challenging topic. A cationic cyclopeptide named TD-34 (ACSSKKSKHCG) was reported to improve insulin delivery across biomembranes effectively. Based on our previous work, we investigated the mechanism of TD-34 for enhancing insulin across Caco-2 cell monolayers. Transport studies of insulin, TD-34 and insulin accompanied with TD-34 were performed respectively using Caco-2 cell monolayers at different conditions. Transepithelial electrical resistance (TEER) value was monitored for 24h immediately after the beginning of transport experiments. Moreover, the tight junction protein (Claudin-1) was localized by confocal immunofluorescence microscopy. Results showed the transport of insulin alone across biomembranes was attributable to multiple routes including passive diffusion. When TD-34 accompanied with or without insulin was treated on Caco-2 cell monolayers, TEER values decreased reversibly, and it was correlated with the reappearance of tight junction proteins by immunostaining assay. It was concluded that the cationic cyclopeptide (TD-34) had the potential to enhance paracellular delivery of insulin across Caco-2 cell monolayers by loosening tight junction reversibly.

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