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Design and synthesis of dual-ligand modified chitosan as a liver targeting vector

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Abstract

Vector plays an important role in hepatic targeted drug delivery system. In this study, a novel material as a liver targeting vector, dual-ligand modified chitosan (GCGA) composed of chitosan (CTS), glycyrrhetinic acid (GA) and lactobionic acid (LA), was designed and synthesized by an orthogonal experiment with two-step synthesis under mild conditions. The synthesized final product was characterized and confirmed by FTIR and 1H-NMR spectroscopy, and DS of GA and LA in CTS were measured to be 13.77 and 16.74 mol% using 1H-NMR, respectively. The cytotoxicity of CTS and GCGA was concentration dependent which was inverse proportion to the cell viability by MTT assay using L929 cell line, and inhibitory concentration 50% (IC50) was 0.2 mg/ml for GCGA. The in vitro targeting efficiency and the in vitro cellular uptake were investigated. Compared with CTS NPs and GA-CTS NPs, GCGA NPs showed good cell specificity to BEL-7402 cells via the dual-ligand-receptor-mediated recognition, leading to a higher affinity to BEL-7402 cells. The results suggested that GCGA described here has the potential to be used as an effective vector for hepatic targeted drug therapy.

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Acknowledgment

We would like to thank the financial support from Self-determined and Innovate Research Funds of Wut (NO. 2010-ZY-CL-042).

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Authors and Affiliations

  1. Biomedical Materials and Engineering Center, Wuhan University of Technology, Wuhan, 430070, People’s Republic of China

    Houxiang Chen & Tao Wan

  2. Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China

    Min Li & Qichang Zheng

  3. Department of General Surgery, Shanghai Fifth People’s Hospital, Fudan University, Shanghai, 200240, People’s Republic of China

    Mingrong Cheng

  4. School of Materials Science and Engineering, Wuhan University of Technology, Wuhan, 430070, People’s Republic of China

    Shiqi Huang & Yong Wang

Authors
  1. Houxiang Chen
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  2. Min Li
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  3. Tao Wan
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  4. Qichang Zheng
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  5. Mingrong Cheng
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  7. Yong Wang
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Correspondence to Tao Wan or Qichang Zheng.

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Houxiang Chen and Min Li contributions by the two collaborating parties are equal.

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Chen, H., Li, M., Wan, T. et al. Design and synthesis of dual-ligand modified chitosan as a liver targeting vector. J Mater Sci: Mater Med 23, 431–441 (2012). https://doi.org/10.1007/s10856-011-4494-1

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  • DOI: https://doi.org/10.1007/s10856-011-4494-1

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