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Docetaxel-loaded D-α-tocopheryl polyethylene glycol-1000 succinate liposomes improve lung cancer chemotherapy and reverse multidrug resistance

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Abstract

In this study, D-alpha-tocopheryl polyethylene glycol-1000 succinate (TPGS)–coated docetaxel-loaded liposomes were developed to reverse multidrug resistance (MDR) and enhance lung cancer therapy. Evaluations were performed using human lung cancer A549 and resistant A549/DDP cells. The reversal multidrug resistant effect was assessed by P-gp inhibition assay, cytotoxicity, cellular uptake, and apoptosis assay. The tumor xenograft model was built by subcutaneous injection of A549/DDP cells in the right dorsal area of nude mice. The tumor volumes and body weights were measured every other day. The TPGS-coated liposomes showed a concentration- and time-dependent cytotoxicity and significantly enhanced the cytotoxicity of docetaxel in A549/DDP cells. Confocal laser scanning images indicated that higher concentrations of coumarin-6 were successfully delivered into the cytoplasm, and the TPGS-coated liposomes enhanced intracellular drug accumulation by inhibiting overexpressed P-glycoprotein. The TPGS-coated liposomes were shown to induce apoptosis. Furthermore, in vivo anti-tumor studies revealed that TPGS-coated docetaxel-loaded liposomes had outstanding anti-tumor efficacy in an A549/DDP xenograft model. The TPGS-coated liposomes, compared with PEG-coated liposomes, showed significant advantages in vitro and in vivo. The TPGS-coated liposomes were able to reverse MDR and enhance lung cancer therapy.

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Correspondence to Jianhong Yang.

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All animal studies were performed in compliance with the guidelines outlined in the Guide for the Care and Use of Laboratory Animals. All animal experiments were reviewed and approved by the Animal Experiment Ethics Committee of Ningxia Medical University.

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The authors declare that they have no conflicts of interest.

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Li, N., Mai, Y., Liu, Q. et al. Docetaxel-loaded D-α-tocopheryl polyethylene glycol-1000 succinate liposomes improve lung cancer chemotherapy and reverse multidrug resistance. Drug Deliv. and Transl. Res. (2020). https://doi.org/10.1007/s13346-020-00720-9

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Keywords

  • Liposomes
  • Docetaxel
  • TPGS
  • Multidrug resistance
  • Lung cancer