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Functionalized docetaxel-loaded lipid-based-nanosuspensions to enhance antitumor efficacy in vivo

Authors Pang X, Wang T, Jiang D, Mu W, Zhang B, Zhang N

Received 18 October 2018

Accepted for publication 18 March 2019

Published 11 April 2019 Volume 2019:14 Pages 2543—2555


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 3

Editor who approved publication: Dr Lei Yang

Xiuping Pang, Tianqi Wang, Dandan Jiang, Weiwei Mu, Bo Zhang, Na Zhang

School of Pharmaceutical Sciences, Key Laboratory of Chemical Biology (Ministry of Education), Shandong University, Jinan, Shandong Province 250012, Peoples’ Republic of China

Purpose: To further enhance the antitumor efficacy through targeted delivery, DTX loaded lipid-based-nanosuspensions (DTX-LNS) were prepared and functionalized by PEGylation or NGR modification to develop DSPE-PEG2000 modified DTX-LNS (P-DTX-LNS) or DSPE-PEG2000-NGR modified DTX-LNS (N-DTX-LNS), respectively.
Methods: Based on our previous work, functionalized DTX-LNS including P-DTX-LNS and N-DTX-LNS were prepared using thin-film hydration, and then characterized. Release behavior, stability in vitro, cytotoxicity and cellular uptake of functionalized LNS were observed. To demonstrate tumor targeting efficiency of functionalized DTX-LNS, in vivo real-time and ex vivo imaging study were conducted. Furthermore, therapeutic efficacy in vivo was evaluated in an H22-bearing mice model.
Results: Functionalized DTX-LNS 100–110 nm in diameter were successfully prepared and exhibited good stability under various conditions. In vitro release studies demonstrated that DTX was released from functionalized DTX-LNS steadily and reached approximately 95% at 48 hrs. Functionalized DTX-LNS showed dose-dependent cytotoxicity and time-dependent internalization in human hepatocellular liver carcinoma cells (HepG2) cells. In vivo real-time and ex vivo imaging results indicated that tumor targeting efficiencies of P-DiR-LNS and N-DiR-LNS were 29.9% and 34.3%, respectively. Moreover, evaluations of in vivo antitumor efficacy indicated that functionalized DTX-LNS effectively inhibited tumor growth with low toxicity.
Conclusion: The functionalized LNS exhibited suitable particle size, nearly spherical structure, enough drug loading and great potentials for large-scale production. The results in vitro and in vivo demonstrated that functionalized LNS could realize tumor targeting and antitumor efficacy. Consequently, functionalized DTX-LNS could be expected to be used for tumor targeting therapy.

Keywords: docetaxel, lipid-based-nanosuspensions, NGR, PEG, nanocarriers

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