期刊
CARBOHYDRATE POLYMERS
卷 157, 期 -, 页码 596-602出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.carbpol.2016.10.021
关键词
Surface charge; CMCS/CS nanoparticles; Insulin oral; Tight junction; Claudin-4
资金
- National Natural Science Foundation of China [31300786, 31500807]
- Applied Basic Research Plan of Qingdao [14-2-4-98-jch]
- National Science Foundation for Post-doctor [2014M560579]
- Promotive Research Fund for Young and Middle-aged Scientists of Shandong Province [BS2015SW010]
- National Natural Science Foundation of China NSFC-Shandong joint fund [U1406402-5]
- Taishan Scholar Program, China
Intestinal epithelium is a major barrier limiting the absorption of oral insulin owing to the presence of intercellular tight junctions (Tjs). Previous studies proved that carboxymethyl chitosan/chitosan-nanoparticles (CMCS/CS-NPs) exhibited surface charge depending promotion of intestinal absorption. This study further confirmed the better performances of insulin:CMCS/CS-NPs(-) in enhancing epithelial permeation, increasing bioavailability and extending blood duration of insulin than insulin:CMCS/CS-NPs(+). Immunohistochemistry sections found that Tjs on jejunum epithelium completely disappeared in insulin:CMCS/CS-NPs(-) group, partially existed in insulin:CMCS/CS-NPs(+) group and appeared no change in control. Surface charges of CMCS/CS-NPs triggered intestinal epithelial TJs opening through different mechanisms. Although a down-regulation of TJs protein claudin-4 was detected in both nanoparticles groups, for phosphorylated claudin-4, the activating form, whose down-regulation occurred only in insulin:CMCS/CS-NPs(-) group. Counting upon synergetic effects of Ca2+ deprivation from adherens junctions and claudin-4 dephosphorylation and degradation, CMCS/CS-NPs(-) triggered more extensive disintegration of Tjs and stronger paracellular permeability than the positive. (C) 2016 Elsevier Ltd. All rights reserved.
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