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Co-disposition of chitosan nanoparticles by multi types of hepatic cells and their subsequent biological elimination: the mechanism and kinetic studies at the cellular and animal levels

Authors Jiang LQ, Wang TY, Wang Y, Wang ZY, Bai YT

Received 12 March 2019

Accepted for publication 3 July 2019

Published 31 July 2019 Volume 2019:14 Pages 6035—6060

DOI https://doi.org/10.2147/IJN.S208496

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 3

Editor who approved publication: Dr Linlin Sun


Li-Qun Jiang,1 Ting-Yu Wang,1 Yun Wang,1 Zi-Yao Wang,1 Yu-Ting Bai1,2

1Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, School of Pharmacy, Xuzhou Medical University, Xuzhou, China; 2School of Stomatology, Xuzhou Medical University, Xuzhou, China

Background: The clearance of nanomaterials (NMs) from the liver is essential for clinical safety, and their hepatic clearance is primarily determined by the co-disposition process of various types of hepatic cells. Studies of this process and the subsequent clearance routes are urgently needed for organic NMs, which are used as drug carriers more commonly than the inorganic ones.
Materials and methods: In this study, the co-disposition of chitosan-based nanoparticles (CsNps) by macrophages and hepatocytes at both the cellular and animal levels as well as their subsequent biological elimination were investigated. RAW264.7 and Hepa1-6 cells were used as models of Kupffer cells and hepatocytes, respectively.
Results: The cellular studies showed that CsNps released from RAW264.7 cells could enter Hepa1-6 cells through both clathrin- and caveolin-mediated endocytosis. The transport from Kupffer cells to hepatocytes was also studied in mice, and it was observed that most CsNps localized to the hepatocytes after intravenous injection. Following the distribution in hepatocytes, the hepatobiliary–fecal excretion route was shown to be the primary elimination route for CsNps, besides the kidney–urinary excretion route. The elimination of CsNps in mice was a lengthy process, with a half time of about 2 months.
Conclusion: The demonstration in this study of the transport of CsNps from macrophages to hepatocytes and the subsequent hepatobiliary–fecal excretion provides basic information for the future development and clinical application of NMs.

Keywords: chitosan nanoparticles, hepatocytes, macrophages, disposition, hepatobiliary–fecal elimination


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