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Preparation, characterization, and evaluation of the antitumor effect of kaempferol nanosuspensions

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Abstract

Kaempferol (KAE) is a naturally occurring flavonoid compound with antitumor activity. However, the low aqueous solubility, poor chemical stability, and suboptimal bioavailability greatly restrict its clinical application in cancer therapy. To address the aforementioned limitations and augment the antitumor efficacy of KAE, we developed a kaempferol nanosuspensions (KAE-NSps) utilizing D-α-tocopherol polyethylene glycol 1000 succinate (TPGS) as a stabilizing agent, screened the optimal preparation process, and conducted a comprehensive investigation of their fundamental properties as well as the antitumor effects in the study. The findings indicated that the particle size was 186.6 ± 2.6 nm of the TPGS-KAE-NSps optimized, the shape of which was fusiform under the transmission electron microscope. The 2% (w/v) glucose was used as the cryoprotectant for TPGS-KAE-NSps, whose drug loading content was 70.31 ± 2.11%, and the solubility was prominently improved compared to KAE. The stability and biocompatibility of TPGS-KAE-NSps were favorable and had a certain sustained release effect. Moreover, TPGS-KAE-NSps clearly seen to be taken in the cytoplasm exhibited a stronger cytotoxicity and suppression of cell migration, along with increased intracellular ROS production and higher apoptosis rates compared to KAE in vitro cell experiments. In addition, TPGS-KAE-NSps had a longer duration of action in mice, significantly improved bioavailability, and showed a stronger inhibition of tumor growth (the tumor inhibition rate of high dose intravenous injection group was 68.9 ± 1.46%) than KAE with no obvious toxicity in 4T1 tumor-bearing mice. Overall, TPGS-KAE-NSps prepared notably improved the defect and the antitumor effects of KAE, making it a promising nanodrug delivery system for KAE with potential applications as a clinical antitumor drug.

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Acknowledgements

The authors thank Mengjing Li from Shiyanjia Lab (www.shiyanjia.com) for the TG-DSC test. The authors are also thankful to Dr. Xue Xu for his technical support to HPLC.

Funding

This work was supported by the National Natural Science Foundation of China (11575107, 81922037, 22003038, and 21371115), the Shanghai University-Universal Medical Imaging Diagnostic Research Foundation (19H00100), and the Shanghai Biomedical Science and Technology Support Project (19441903600).

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Author notes

  1. Wen He and Junfeng Zhang are first authors to this work.

Authors and Affiliations

  1. Institution of Nanochemistry and Nanobiology, School of Environmental and Chemical Engineering, Shanghai University, Shanghai, 200444, China

    Wen He, Junfeng Zhang, Yinghua Wu, Yuxi Zhang, Lin Zhan, Chenchen Li & Yanli Wang

  2. School of Medicine, Shanghai University, Shanghai, 200444, China

    Wen He, Jiale Ju & Yanli Wang

  3. Key Laboratory of Tropical Translation Medicine of Ministry of Education, Hainan Provincial Key Laboratory for Research and Development of Tropical Herbs, School of Pharmacy, Hainan Medical University, Haikou, 571199, China

    Yanli Wang

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  1. Wen He
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Contributions

Work conception and design: Wen He, Chenchen Li, and Yanli Wang; writing, original draft: Wen He and Junfeng Zhang; writing, review and editing: Chenchen Li and Yanli Wang; material synthesis and characterization: Wen He and Lin Zhan; cell experiment: Wen He, Yinghua Wu, and Jiale Ju; animal experiment: Wen He, Junfeng Zhang, and Yuxi Zhang.

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Correspondence to Chenchen Li or Yanli Wang.

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All animal experiments were performed in accordance with the National Regulations of China for the Care and Use of Laboratory Animals and were approved by the Shanghai University Animal Care and Use Institutional Committee.

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He, W., Zhang, J., Ju, J. et al. Preparation, characterization, and evaluation of the antitumor effect of kaempferol nanosuspensions. Drug Deliv. and Transl. Res. 13, 2885–2902 (2023). https://doi.org/10.1007/s13346-023-01357-0

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