β-Cyclodextrin-Grafted Chitosan Enhances Intestinal Drug Absorption and Its Preliminary Mechanism Exploration
β-Cyclodextrin (CD) and chitosan (CS) have attracted great attention due to their unique properties and structures. β-Cyclodextrin-grafted chitosan (CD-CS) has been widely used as a drug carrier to prepare nano-formulations for drug delivery. However, few researches have been conducted to investigat...
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| Veröffentlicht in: | AAPS PharmSciTech 2022-08, Vol.23 (6), p.221-221, Article 221 |
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| creator | Zou, Linghui Zhang, Zhongbin Chen, Jinqing Yang, Xu Li, Yuyang Tang, Jing Du, Xiaolu Tang, Ling Liang, Dan Zhu, Xiaoyong Feng, Jianfang Ding, Wenya |
| description | β-Cyclodextrin (CD) and chitosan (CS) have attracted great attention due to their unique properties and structures. β-Cyclodextrin-grafted chitosan (CD-CS) has been widely used as a drug carrier to prepare nano-formulations for drug delivery. However, few researches have been conducted to investigate the effect of CD-CS as an excipient on cellular uptake and intestinal absorption. Herein, Caco-2 cells were used to investigate the influence of CD-CS on cellular uptake. The MTT assay showed that CD-CS was non-toxic to Caco-2 cells in concentrations ranging from 15.62 to 125 μg/mL. Confocal laser microscopy and flow cytometry measurements indicated that the uptake ability of Caco-2 cells was significantly enhanced after being treated with CD-CS at a concentration of 31.25 μg/mL or incubation for 0.5 h, and the uptake enhancement gradually increased with increasing CD-CS concentration and incubation time. The Caco-2 monolayer cell model and the everted intestinal sac method were employed to preliminarily explore the mechanism of the improved intestinal absorption. The results demonstrated that CD-CS might open the tight junctions and enhance the clathrin-dependent endocytosis, macro-pinocytosis, and phagocytosis of the intestinal epithelial cells. Such findings can serve as references and inspiration for the design of absorption enhancers.
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| doi_str_mv | 10.1208/s12249-022-02380-z |
| format | Article |
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Graphical abstract</description><subject>Biochemistry</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Biotechnology</subject><subject>Pharmacology/Toxicology</subject><subject>Pharmacy</subject><subject>Research Article</subject><subject>Theme: Advancements in Modified-release Oral Drug Delivery - Delivery throughout the Gastro-intestinal Tract</subject><issn>1530-9932</issn><issn>1530-9932</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><recordid>eNp9kL1OwzAQxy0EEqXwAkweWQz-yIczVqGUSkUwwGw5idO6Suxgu1LpY_EgPBMuYWBiON0Nv__p7gfANcG3hGJ-5wmlSYEwpbEYx-hwAiYkZRgVBaOnf-ZzcOH9FkeKFGwCzNcnKj_qzjZqH5w2aOFkG1QDy40O1ksD52YjTa08XJqgfNBGdvDe7dZwVnnrhqCtgdI0cBk8fHGq031E3Ad8UnUMat_D-X7orJNH8hKctbLz6uq3T8Hbw_y1fESr58WynK1QTdMkoDSnecZTnrSJTDLGaVGljaqkanjNJJZMKsqLJFepbAvGZJvmkrKKcYJxThlmU3Az7h2cfd_Fs0Wvfa26Thpld17QHJNIJlkWUTqitbPeO9WKwek-fiAIFke5YpQrolzxI1ccYoiNIR9hs1ZObO3ORTX-v9Q3t1R_XA</recordid><startdate>20220810</startdate><enddate>20220810</enddate><creator>Zou, Linghui</creator><creator>Zhang, Zhongbin</creator><creator>Chen, Jinqing</creator><creator>Yang, Xu</creator><creator>Li, Yuyang</creator><creator>Tang, Jing</creator><creator>Du, Xiaolu</creator><creator>Tang, Ling</creator><creator>Liang, Dan</creator><creator>Zhu, Xiaoyong</creator><creator>Feng, Jianfang</creator><creator>Ding, Wenya</creator><general>Springer International Publishing</general><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20220810</creationdate><title>β-Cyclodextrin-Grafted Chitosan Enhances Intestinal Drug Absorption and Its Preliminary Mechanism Exploration</title><author>Zou, Linghui ; Zhang, Zhongbin ; Chen, Jinqing ; Yang, Xu ; Li, Yuyang ; Tang, Jing ; Du, Xiaolu ; Tang, Ling ; Liang, Dan ; Zhu, Xiaoyong ; Feng, Jianfang ; Ding, Wenya</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c254t-572768584f4a463829b5debaed8c3a0a3ae28947e5af933af57a23b3810072303</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Biochemistry</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Biotechnology</topic><topic>Pharmacology/Toxicology</topic><topic>Pharmacy</topic><topic>Research Article</topic><topic>Theme: Advancements in Modified-release Oral Drug Delivery - Delivery throughout the Gastro-intestinal Tract</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zou, Linghui</creatorcontrib><creatorcontrib>Zhang, Zhongbin</creatorcontrib><creatorcontrib>Chen, Jinqing</creatorcontrib><creatorcontrib>Yang, Xu</creatorcontrib><creatorcontrib>Li, Yuyang</creatorcontrib><creatorcontrib>Tang, Jing</creatorcontrib><creatorcontrib>Du, Xiaolu</creatorcontrib><creatorcontrib>Tang, Ling</creatorcontrib><creatorcontrib>Liang, Dan</creatorcontrib><creatorcontrib>Zhu, Xiaoyong</creatorcontrib><creatorcontrib>Feng, Jianfang</creatorcontrib><creatorcontrib>Ding, Wenya</creatorcontrib><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>AAPS PharmSciTech</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zou, Linghui</au><au>Zhang, Zhongbin</au><au>Chen, Jinqing</au><au>Yang, Xu</au><au>Li, Yuyang</au><au>Tang, Jing</au><au>Du, Xiaolu</au><au>Tang, Ling</au><au>Liang, Dan</au><au>Zhu, Xiaoyong</au><au>Feng, Jianfang</au><au>Ding, Wenya</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>β-Cyclodextrin-Grafted Chitosan Enhances Intestinal Drug Absorption and Its Preliminary Mechanism Exploration</atitle><jtitle>AAPS PharmSciTech</jtitle><stitle>AAPS PharmSciTech</stitle><date>2022-08-10</date><risdate>2022</risdate><volume>23</volume><issue>6</issue><spage>221</spage><epage>221</epage><pages>221-221</pages><artnum>221</artnum><issn>1530-9932</issn><eissn>1530-9932</eissn><abstract>β-Cyclodextrin (CD) and chitosan (CS) have attracted great attention due to their unique properties and structures. β-Cyclodextrin-grafted chitosan (CD-CS) has been widely used as a drug carrier to prepare nano-formulations for drug delivery. However, few researches have been conducted to investigate the effect of CD-CS as an excipient on cellular uptake and intestinal absorption. Herein, Caco-2 cells were used to investigate the influence of CD-CS on cellular uptake. The MTT assay showed that CD-CS was non-toxic to Caco-2 cells in concentrations ranging from 15.62 to 125 μg/mL. Confocal laser microscopy and flow cytometry measurements indicated that the uptake ability of Caco-2 cells was significantly enhanced after being treated with CD-CS at a concentration of 31.25 μg/mL or incubation for 0.5 h, and the uptake enhancement gradually increased with increasing CD-CS concentration and incubation time. The Caco-2 monolayer cell model and the everted intestinal sac method were employed to preliminarily explore the mechanism of the improved intestinal absorption. The results demonstrated that CD-CS might open the tight junctions and enhance the clathrin-dependent endocytosis, macro-pinocytosis, and phagocytosis of the intestinal epithelial cells. Such findings can serve as references and inspiration for the design of absorption enhancers.
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| subjects | Biochemistry Biomedical and Life Sciences Biomedicine Biotechnology Pharmacology/Toxicology Pharmacy Research Article Theme: Advancements in Modified-release Oral Drug Delivery - Delivery throughout the Gastro-intestinal Tract |
| title | β-Cyclodextrin-Grafted Chitosan Enhances Intestinal Drug Absorption and Its Preliminary Mechanism Exploration |
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