Enhancement of Drug Absorption through the Blood-Brain Barrier and Inhibition of Intercellular Tight Junction Resealing by E-Cadherin Peptides

Paul Kiptoo, - and Ernawati Sinaga, - and Anna M. Calcagno, - and Hong Zhao, - and Naoki Kobayashi, - and Usman S. F. Tambunan, - and Teruna J. Siahaan, - (2011) Enhancement of Drug Absorption through the Blood-Brain Barrier and Inhibition of Intercellular Tight Junction Resealing by E-Cadherin Peptides. MOLECULAR PHARMACEUTICS, 8 (1). pp. 239-240.

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Abstract

E-cadherin-mediated cell-cell interactions in the zonula adherens play an important role in the formation of the intercellular tight junctions found in the blood-brain barrier. However, it is also responsible for the low permeation of drugs into the brain. In this study, HAV6 peptide derivedfromtheEC1domainofE-cadherinwasfoundtoenhancethepermeationof 14C-mannitol and [3H(G)]-daunomycin through the blood-brain barrier of the in situ rat brain perfusion model. In addition, HAV6 peptide and verapamil have a synergistic effect in enhancing the BBB permeation of daunomycin. A new intercellular-junction resealing assay was also developed using Caco-2 monolayers to evaluate new peptides (BLG2, BLG3, and BLG4) derived from the bulge regions of the EC2, EC3, and EC4 domains of E-cadherin. BLG2 and BLG4 peptides but not BLG3 peptides were found to be effective in blocking the resealing of the intercellular junctions. The positive control peptides (ADT10, ADT6, and HAV10) block the resealing of the intercellular junctions in a concentration-dependent manner. All these findings suggest that E-cadherin-derivedpeptidescanblockE-cadherin-mediatedcell-cellinteractions.Thesefindings demonstrate that cadherin peptides may offer a useful targeted permeation enhancement of therapeutic agents such as anticancer drugs into the brain. Keywords: E-cadherin; cell-cell adhesion; HAV peptides; ADT peptides; intercellular junctions; adherens junction; Caco-2 cell monolayers

Item Type: Article
Subjects: R Medicine > R Medicine (General)
Divisions: Artikel > Biologi
Depositing User: BPSI Unas
Date Deposited: 30 Aug 2017 05:39
Last Modified: 30 Aug 2017 05:39
URI: http://repository.unas.ac.id/id/eprint/176

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