Novel oral absorption system containing polyamines and bile salts enhances drug transport via both transcellular and paracellular pathways across Caco-2 cell monolayers

Fuyuki Mukaizawa, Koji Taniguchi, Masateru Miyake, Ken ichi Ogawara, Masaaki Odomi, Kazutaka Higaki, Toshikiro Kimura

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

The combinatorial use of spermine (SPM), a typical polyamine, and sodium taurocholate (STC), a typical bile salt, was found to be a promising safe preparation for improving the oral absorption of poorly water-soluble and/or poorly absorbable drug in our previous studies utilizing rats and dogs. To clarify the mechanisms behind the synergistic enhancement effect of the polyamine and bile salt, the transport of rebamipide, which is classified into Biopharmaceutics Classification System Class IV, was investigated in Caco-2 cell monolayers. The synergistic enhancement of rebamipide transport by SPM and STC was certainly observed in Caco-2 cells as well, while the separate use of either SPM or STC did not significantly improve the transport of rebamipide. The combinatorial use of SPM and STC significantly decreased the transepithelial electrical resistance (TEER) in Caco-2 cell monolayers, suggesting that the opening of paracellular pathway. On the other hand, it was also confirmed that the decrease in TEER was transient and reversible after removal of SPM and STC and that cell viability was maintained. Voltage-clamp study clearly showed that their combinatorial use improved rebamipide transport via both paracellular and transcellular pathways, and that the contribution of transcellular route could be larger than paracellular route.

Original languageEnglish
Pages (from-to)103-108
Number of pages6
JournalInternational Journal of Pharmaceutics
Volume367
Issue number1-2
DOIs
Publication statusPublished - Feb 9 2009

Fingerprint

Transcytosis
Taurocholic Acid
Caco-2 Cells
Spermine
Polyamines
Bile Acids and Salts
Pharmaceutical Preparations
Electric Impedance
Biopharmaceutics
Cell Survival
Dogs
rebamipide
Water

Keywords

  • Caco-2 cells
  • Electrophysiological study
  • Sodium taurocholate
  • Spermine
  • Transport pathways

ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

Novel oral absorption system containing polyamines and bile salts enhances drug transport via both transcellular and paracellular pathways across Caco-2 cell monolayers. / Mukaizawa, Fuyuki; Taniguchi, Koji; Miyake, Masateru; Ogawara, Ken ichi; Odomi, Masaaki; Higaki, Kazutaka; Kimura, Toshikiro.

In: International Journal of Pharmaceutics, Vol. 367, No. 1-2, 09.02.2009, p. 103-108.

Research output: Contribution to journalArticle

Mukaizawa, Fuyuki ; Taniguchi, Koji ; Miyake, Masateru ; Ogawara, Ken ichi ; Odomi, Masaaki ; Higaki, Kazutaka ; Kimura, Toshikiro. / Novel oral absorption system containing polyamines and bile salts enhances drug transport via both transcellular and paracellular pathways across Caco-2 cell monolayers. In: International Journal of Pharmaceutics. 2009 ; Vol. 367, No. 1-2. pp. 103-108.
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