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β-Cyclodextrin-Grafted Chitosan Enhances Intestinal Drug Absorption and Its Preliminary Mechanism Exploration

  • Research Article
  • Advancements in Modified-release Oral Drug Delivery: Delivery Throughout the Gastro-intestinal tract
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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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Funding

This research was supported by the National Natural Science Foundation of China (No. 82060806), China Postdoctoral Science Foundation (2019BS006), Graduate Education Innovation Program of Guangxi University of Chinese Medicine (YCSZ2022008), Research and Training Project of College Students in Guangxi University of Chinese Medicine (2021DXS09), and Qihuang High-Level Talent Team Cultivation Project of Guangxi University of Chinese Medicine (2021002).

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Author notes

  1. Linghui Zou, Zhongbin Zhang And Jinqing Chen contributed to the work equally and are co-first authors.

Authors and Affiliations

  1. College of Pharmacy, Guangxi University of Chinese Medicine, Nanning, China

    Linghui Zou, Jinqing Chen, Xu Yang, Yuyang Li, Jing Tang, Xiaolu Du, Ling Tang, Dan Liang, Xiaoyong Zhu, Jianfang Feng & Wenya Ding

  2. College of Basic Medicine, Guangxi University of Chinese Medicine, Nanning, China

    Zhongbin Zhang

  3. Key Laboratory of Common Technology of Chinese Medicine Preparations, Guangxi University of Chinese Medicine, Nanning, China

    Dan Liang, Jianfang Feng & Wenya Ding

  4. South China Branch of National Engineering Research Center for Manufacturing Technology of Traditional Chinese Medicine Solid Preparation, Nanning, China

    Jianfang Feng & Wenya Ding

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  1. Linghui Zou
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Contributions

Linghui Zou, Zhongbin Zhang, and Jinqing Chen performed the experiments and analyzed the data, and Linghui Zou was the major contributor in writing the original manuscript. Xu Yang, Yuyang Li, Jing Tang, Xiaolu Du, and Ling Tang prepared figures for the manuscript. Dan Liang, Jianfang Feng, Xiaoyong Zhu, and Wenya Ding conceptualized, reviewed, and edited the original manuscript.

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Correspondence to Wenya Ding.

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Zou, L., Zhang, Z., Chen, J. et al. β-Cyclodextrin-Grafted Chitosan Enhances Intestinal Drug Absorption and Its Preliminary Mechanism Exploration. AAPS PharmSciTech 23, 221 (2022). https://doi.org/10.1208/s12249-022-02380-z

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