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Inclusion complex of emodin and glycyrrhetinic acid-conjugated-β-cyclodextrin to target liver cells: synthesis, characterization, and bioactivity in vitro and in vivo

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Abstract

The objective of this study is to prepare a novel delivery vector, glycyrrhetinic acid -conjugated-β-cyclodextrin (GA-CD) for liver targeting, and investigate the effects of the emodin-GA-CD inclusion complex (E-GA-CD complex) on liver cancer therapy. GA-CD was synthesized from GA and CD, and was used to encapsulate emodin to form an E-GA-CD complex. Proton nuclear magnetic resonance spectroscopy, two-dimensional rotating-frame Overhauser effect spectroscopy, and differential scanning calorimetry were used to characterize GA-CD and the E-GA-CD complex. Liver cell targeting bioactivity of the E-GA-CD complex was investigated by cellular uptake, cell viability, and biodistribution. In vitro results revealed that the E-GA-CD complex exhibited increased cellular uptake and cytotoxicity against Hep3B cells compared to free emodin. In vivo biodistribution results indicated that mice treated with the E-GA-CD complex exhibited greater emodin uptake in liver tissue than emodin-treated mice, suggesting that the E-GA-CD complex was effective in targeting liver cells.

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Acknowledgements

The authors would like to thank Professor Lei Wan at China Med-ical University for cell culture technique support. This work was partially supported by the grants from China Medical University (CMU104-S-53 and CMU106-S-08).

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Authors and Affiliations

  1. Graduate Institute of Chinese Medicine, China Medical University, Taichung, Taiwan

    Song-Cu Yu, Yi-Ting Hou & Yuhsin Tsai

  2. School of Chinese Medicine, China Medical University, No.91 Hsueh-Shih Road, Taichung, Taiwan

    Song-Cu Yu & Yuhsin Tsai

  3. Division of Hematology & Oncology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan

    Chin-Mu Hsu

  4. Department of Medical Research, China Medical University Hospital, Taichung, Taiwan

    Fuu-Jen Tsai

  5. Department of Medical Genetics, Pediatrics and Medical Research, China Medical University Hospital, Taichung, Taiwan

    Fuu-Jen Tsai

  6. Department of Biotechnology, Asia University, Taichung, Taiwan

    Fuu-Jen Tsai

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  1. Song-Cu Yu
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  2. Yi-Ting Hou
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Correspondence to Yuhsin Tsai.

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Yu, SC., Hou, YT., Hsu, CM. et al. Inclusion complex of emodin and glycyrrhetinic acid-conjugated-β-cyclodextrin to target liver cells: synthesis, characterization, and bioactivity in vitro and in vivo. J Incl Phenom Macrocycl Chem 102, 339–346 (2022). https://doi.org/10.1007/s10847-021-01123-0

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  • DOI: https://doi.org/10.1007/s10847-021-01123-0

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