A potential mechanism of a cationic cyclopeptide for enhancing insulin delivery across Caco-2 cell monolayers.
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 24 h 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.
School of Pharmaceutical Science and Technology, Dalian University of Technology.
Mingming
M
Chang
Xiaohui
X
Li
Yuming
Y
Sun
Fang
F
Cheng
Yueqing
Y
Li
Weijie
W
Zhao
Qing
Q
Wang
D001692:Biological Transport; D018938:Caco-2 Cells; D002412:Cations / Q000494:pharmacology*; D002463:Cell Membrane Permeability / Q000187:drug effects*; D062445:Claudin-1 / Q000378:metabolism; D016503:Drug Delivery Systems; D006801:Humans; D007328:Insulin / Q000008:administration & dosage* / Q000378:metabolism; D010456:Peptides, Cyclic / Q000494:pharmacology*; D062725:Tight Junction Proteins / Q000378:metabolism*; D019108:Tight Junctions / Q000187:drug effects* / Q000378:metabolism
D002412:Cations; D062445:Claudin-1; D007328:Insulin; D010456:Peptides, Cyclic; D062725:Tight Junction Proteins