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Amphiphilically modified chitosan cationic nanoparticles for drug delivery

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Abstract

A series of amphiphilic N-(2-hydroxy)propyl-3-trimethylammonium-chitosan-cholic acid (HPTA-CHI-CA) polymers were synthesized by grafting cholic acid (CA) and glycidyltrimethylammonium chloride onto chitosan. The self-assembly behavior of HPTA-CHI-CA was studied by fluorescence technique. The polymers were able to self-assemble into NPs in phosphate buffered saline with a critical aggregation concentration (CAC) in the range of 66–26 mg/L and the CAC decreased with the increasing of the degree of substitution (DS) of CA. The size of cationic HPTA-CHI-CA NPs ranges from 170 to 220 nm (PDI < 0.2). It was found that doxorubicin (DOX) could be encapsulated into HPTA-CHI-CA NPs based on self-assembly. The drug loading content and efficiency varies depending on the DS of CA and feeding ratio of DOX to polymer. In vitro release studies suggested that DOX released slowly from HPTA-CHI-CA NPs without any burst initial release. Besides, the confocal microscopic measurements indicated that DOX-HPTA-CHI-CA NPs could easily be uptaken by breast cancer (MCF-7) cells and release DOX in cytoplasm. Anti-tumor efficacy results showed that DOX-HPTA-CHI-CA NPs have a significant activity of inhibition MCF-7 cells growth. These results suggest cationic HPTA-CHI-CA may have great potential for anticancer drug delivery.

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Acknowledgments

This work was supported by National Natural Science Foundation of China Grant 81072405, Zhejiang Provincial Natural Science Foundation Grants R2100528 and LY12H31003, and Zhejiang Provincial Program for the Cultivation of High level Innovative Health talents and for Innovative Research Team in Zhejiang Province Grant 2010R50046.

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Authors and Affiliations

  1. Department of Oncology, The First Affiliated Hospital of Wenzhou Medical College, Wenzhou, 325035, China

    Jie You, Chang Yu, Langping Jin, Yili Zhou, Xuzhong Xu, Siyang Dong & Ouchen Wang

  2. Department of Radiotherapy and Chemotherapy, The First Affiliated Hospital of Wenzhou Medical College, Wenzhou, 325035, China

    Wenfeng Li

  3. Department of Pharmacy, Wenzhou Medical College, Wenzhou, 325035, China

    Chengguang Zhao

  4. Institute of Genomic Medicine, Wenzhou Medical College, Wenzhou, 325035, China

    Xincheng Lu

Authors
  1. Jie You
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  2. Wenfeng Li
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  3. Chang Yu
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  4. Chengguang Zhao
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  5. Langping Jin
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  6. Yili Zhou
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  7. Xuzhong Xu
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  8. Siyang Dong
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  9. Xincheng Lu
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  10. Ouchen Wang
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Correspondence to Ouchen Wang.

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You, J., Li, W., Yu, C. et al. Amphiphilically modified chitosan cationic nanoparticles for drug delivery. J Nanopart Res 15, 2123 (2013). https://doi.org/10.1007/s11051-013-2123-2

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