Permeability of Exendin-4-Loaded Chitosan Nanoparticles across MDCK Cell Monolayers and Rat Small Intestine
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- Wang Mengshu
- National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University
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- Zhang Yong
- National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University Key Laboratory for Molecular Enzymology and Engineering, the Ministry of Education, School of Life Sciences, Jilin University
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- Sun Bingxue
- National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University
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- Sun Yanan
- National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University
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- Gong Xin
- National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University
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- Wu Yongge
- National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University
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- Zhang Xizhen
- National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University
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- Kong Wei
- National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University Key Laboratory for Molecular Enzymology and Engineering, the Ministry of Education, School of Life Sciences, Jilin University
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- Chen Yan
- National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University Key Laboratory for Molecular Enzymology and Engineering, the Ministry of Education, School of Life Sciences, Jilin University
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The purpose of this study was to investigate the permeability of exendin-4-loaded chitosan nanoparticles using the Madin Darby canine kidney (MDCK) cell monolayer as an in vitro model and the rat intestine as an ex vivo model of the human intestinal barrier. A series of formulations of sodium tripolyphosphate (TPP) and chitosan with different molecular weights and degrees of deacetylation was evaluated. The formulation consisting of 0.1% TPP and 0.2% chitosan (400 kDa, 95% degree of deacetylation), which gave optimized monodispersed particle size (303.1±10.36 nm), zeta potential (18.37±1.15 mV) and encapsulation efficiency (38.0±2.6%), was used for further analysis. After determining their biocompatibility, the transport potential of drug-loaded chitosan nanoparticles was evaluated and compared with free exendin-4 using both MDCK cell monolayers and different rat intestinal segments. Mechanisms underlying enhanced transport of exendin-4 in the cell model were also explored. Compared with free exendin-4, the absorption of optimized chitosan nanoparticles was enhanced by 4.7-fold in MDCK cell monolayers and by 2.0–2.78-fold in different rat intestinal segments, with no significant difference between the duodenum, jejunum and ileum. As supported by confocal laser scanning microscopic analysis, the lower enhancement of absorption in the intestine compared to the cell monolayer likely resulted from the chitosan nanoparticle-mediated opening of cellular tight junctions and not through intracellular transport. These findings suggest that the potential application of chitosan nanoparticles as delivery carriers of exendin-4 is limited and may need further modifications.
収録刊行物
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- Biological & Pharmaceutical Bulletin
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Biological & Pharmaceutical Bulletin 37 (5), 740-747, 2014
公益社団法人 日本薬学会
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詳細情報 詳細情報について
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- CRID
- 1390001204632463616
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- NII論文ID
- 130004147320
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- NII書誌ID
- AA10885497
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- COI
- 1:STN:280:DC%2BC2cnpsVClsQ%3D%3D
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- ISSN
- 13475215
- 09186158
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- NDL書誌ID
- 025419838
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- PubMed
- 24789997
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- 本文言語コード
- en
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- データソース種別
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- JaLC
- NDL
- Crossref
- PubMed
- CiNii Articles
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- 抄録ライセンスフラグ
- 使用不可