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Synergistic combination therapy of lung cancer using paclitaxel- and triptolide-coloaded lipid–polymer hybrid nanoparticles

Authors Liu J, Cheng H, Han L, Qiang Z, Zhang X, Gao W, Zhao K, Song Y

Received 25 April 2018

Accepted for publication 19 July 2018

Published 25 September 2018 Volume 2018:12 Pages 3199—3209

DOI https://doi.org/10.2147/DDDT.S172199

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 3

Editor who approved publication: Prof. Dr. Cristiana Tanase


Jia Liu,* Hao Cheng,* Le Han, Zhun Qiang, Xinwei Zhang, Wei Gao, Kun Zhao, Yangrong Song

Department of Thoracic Surgery, Tumor Hospital of Shaanxi Province, Xi’an, Shaanxi, People’s Republic of China

*These authors contributed equally to this work

Purpose: Non-small cell lung cancer (NSCLC) accounts for the majority of lung cancer. Lipid–polymer hybrid nanoparticles (LPNs) combine the advantages of both polymeric nanoparticles and liposomes into a single delivery platform. In this study, we engineered LPNs as the co-delivery system of paclitaxel (PTX) and triptolide (TL) to achieve synergistic therapeutic effect and reduced drug resistance.
Materials and methods: In this study, PTX- and TL-coloaded LPNs (P/T-LPNs) were fabricated by nanoprecipitation method using lipid and polymeric materials. The P/T-LPNs combination effects on human lung cancer cells were studied. Therapeutic potentials of P/T-LPNs were further determined using lung cancer cells-bearing mice model.
Results: The average particle sizes of LPNs were around 160 nm, with narrow size distribution below 0.2. The zeta potential value of LPNs was about -30 mV. The encapsulating efficiency (EE) of PTX and TL loaded in LPNs was over 85%. The cytotoxicity of dual drug loaded LPNs was higher than single drug loaded LPNs. The combination therapy showed synergistic when PTX:TL weight ratio was 5:3, indicating the synergy effects of the LPNs. In vivo tumor growth curve of the experimental group was more gentle opposed to the control group, and tumor volumes of P/T-LPNs and control group were 392 and 1,737 mm3, respectively. The inhibition rate on day 20 was 77.4% in the P/T-LPNs group, which is higher than the free drugs solution.
Conclusion: The in vivo and in vitro results proved the synergetic effect of the two drugs coloaded in LPNs on the lung cancer xenografts, with the least systemic toxic side effect.

Keywords: non-small cell lung cancer, multidrug resistance, combination therapy, paclitaxel, triptolide

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