TY - JOUR

T1 - Laurate permeates the paracellular pathway for small molecules in the intestinal epithelial cell model HT-29/B6 via opening the tight junctions by reversible relocation of claudin-5

AU - Dittmann, I.

AU - Amasheh, M.

AU - Krug, S.M.

AU - Markov, A.G.

AU - Fromm, M.

AU - Amasheh, S.

PY - 2014

Y1 - 2014

N2 - Purpose To mechanistically analyze effects of the medium-chain fatty acid laurate on transepithelial permeability in confluent monolayers of the intestinal epithelial cell line HT-29/B6, in context with an application as an absorption enhancer improving transepithelial drug permeation. Methods Transepithelial resistance and apparent ermeability for paracellular flux markers was measured using Ussing-type chambers. Two-path impedance spectroscopy was employed to differentiate between transcellular and paracellular resistance, and confocal imaging and Western blotting was performed. Results Laurate resulted in a substantial and reversible decrease in transepithelial resistance by 50% which was attributed to a decrease in paracellular resistance. Simultaneously, an increase in permeability for fluorescein (330 Da) was detected, while permeabilities for 4 kDa FITC-dextran and sulpho-NHS-SS-biotin (607 Da) remained unaltered. Confocal laser-scanning microscopy revealed a marked reduction of claudin-5, while other

AB - Purpose To mechanistically analyze effects of the medium-chain fatty acid laurate on transepithelial permeability in confluent monolayers of the intestinal epithelial cell line HT-29/B6, in context with an application as an absorption enhancer improving transepithelial drug permeation. Methods Transepithelial resistance and apparent ermeability for paracellular flux markers was measured using Ussing-type chambers. Two-path impedance spectroscopy was employed to differentiate between transcellular and paracellular resistance, and confocal imaging and Western blotting was performed. Results Laurate resulted in a substantial and reversible decrease in transepithelial resistance by 50% which was attributed to a decrease in paracellular resistance. Simultaneously, an increase in permeability for fluorescein (330 Da) was detected, while permeabilities for 4 kDa FITC-dextran and sulpho-NHS-SS-biotin (607 Da) remained unaltered. Confocal laser-scanning microscopy revealed a marked reduction of claudin-5, while other

KW - drug uptake

KW - absorption enchancer

KW - epithelial cell

KW - tight junction

U2 - 10.1007/s11095-014-1350-2

DO - 10.1007/s11095-014-1350-2

M3 - Article

VL - 31

SP - 2539

EP - 2548

JO - Pharmaceutical Research

JF - Pharmaceutical Research

SN - 0724-8741

IS - 9

ER -