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Quaternization of high molecular weight chitosan for increasing intestinal drug absorption using Caco-2 cells as an in vitro intestinal model
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Document Title
Quaternization of high molecular weight chitosan for increasing intestinal drug absorption using Caco-2 cells as an in vitro intestinal model
Author
Wongwanakul R., Aueviriyavit S., Furihata T., Gonil P., Sajomsang W., Maniratanachote R., Jianmongkol S.
Affiliations
Department of Pharmacology and Physiology, Faculty of Pharmaceutical Sciences, Chulalongkorn University, 254 Phayathai Road, Bangkok, 10330, Thailand; National Nanotechnology Center, National Science and Technology Development Agency, 111 Thailand Science Park, Pathum Thani, 12120, Thailand; Laboratory of Pharmacology and Toxicology, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba, Japan; Toxicology and Bio Evaluation Service Center, National Science and Technology Development Agency, Pathum Thani, Thailand
Type
Article
Source Title
Scientific Reports
ISSN
20452322
Year
2023
Volume
13
Issue
1
Page
-
Open Access
All Open Access, Gold
Publisher
Nature Research
DOI
10.1038/s41598-023-34888-0
Format
Abstract
Potential 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. © 2023, The Author(s).
Funding Sponsor
Chulalongkorn University; National Science and Technology Development Agency; Thailand Graduate Institute of Science and Technology
Publication Source
WOS