Author:
Wongwanakul Ratjika,Aueviriyavit Sasitorn,Furihata Tomomi,Gonil Pattarapond,Sajomsang Warayuth,Maniratanachote Rawiwan,Jianmongkol Suree
Abstract
AbstractPotential use of a quaternized chitosan (MW 600 kDa) with 65% of 3-chloro-2-hydroxypropyltrimethylammonium (600-HPTChC65) as an absorptive enhancer was investigated in Caco-2 monolayers. 600-HPTChC65 (0.005% w/v) quickly reduced transepithelial electrical resistance (TEER) to the maximum level in 40 min with full recovery within 6 h after removal. Its TEER reduction was corresponded to increased FD4 transport across the monolayers and disrupted localization of tight junction proteins ZO-1 and occludin at the cell borders. 600-HPTChC65 was densely localized at the membrane surface and intercellular junctions. This chitosan (0.08–0.32% w/v) reduced the efflux ratio of [3H]-digoxin by 1.7- 2 folds, suggesting an increased [3H]-digoxin transport across the monolayers. Its binding with P-gp on Caco-2 monolayer increased the signal of fluorescence-labeled anti-P-gp (UIC2) reactivity due to conformational change. 600-HPTChC65 (0.32% w/v) had no effect on P-gp expression in the Caco-2 monolayers. These results suggest that 600-HPTChC65 could enhance drug absorption through tight junction opening and decreased P-gp function. Its interaction with the absorptive barrier mainly resulted in disrupting ZO-1 and occludin organization as well as changing in P-gp conformation.
Funder
Ratchadaphiseksomphot Endowment Fund of Chulalongkorn University
Chulalongkorn University
Thailand Graduate Institute of Science and Technology
Ratchadaphiseksomphot Endowment Fund of Chulalongkorn University
Publisher
Springer Science and Business Media LLC
Cited by
2 articles.
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