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壳聚糖纳米粒对多种类型肝细胞的联合处置及伴随的生物消除:细胞和动物机制和动力学研究
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-blind
Peer reviewers approved by Dr Thiruganesh Ramasamy
Peer reviewer comments 3
Editor who approved publication: Dr Linlin Sun
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