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Self-Assembled Hydrophobic Honokiol Loaded MPEG-PCL Diblock Copolymer Micelles

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Abstract

Purpose

Honokiol showed potential application in cancer treatment, but its poor water solubility restricts its clinical application greatly. So, we designed a self-assembled monomethoxy poly(ethylene glycol)-poly(ε-caprolactone) (MPEG-PCL) micelle to load honokiol to overcome its poor water solubility.

Methods

We synthesized MPEG-PCL diblock copolymer that could self-assemble into monodisperse micelles at the particle size of ca.18 nm in water. Honokiol was loaded into MPEG-PCL micelle by direct dissolution method assisted by ultrasound, without any surfactants, organic solvents, and vigorous stirring.

Results

The blank MPEG-PCL micelles (100 mg/mL) did not induce any hemolysis in vitro and showed very low toxicity ex vivo and in vivo. Honokiol could be molecularly incorporated into MPEG-PCL micelles at the drug loading of about 20% by direct dissolution method assisted by ultrasound. After loaded into MPEG-PCL micelles, honokiol maintained its molecular structure and anticancer activity in vitro. Honokiol could be sustained released from MPEG-PCL micelles in vitro. The honokiol loaded MPEG-PCL micelles could be lyophilized without any adjuvant.

Conclusion

The prepared honokiol formulation based on self-assembled MPEG-PCL micelle was stable, safe, effective, easy to produce and scale up, and showed potential clinical application.

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Authors and Affiliations

  1. State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, 610041, China

    MaLing Gou, XiuLing Zheng, Ke Men, Juan Zhang, BiLan Wang, Lei Lv, XiuHong Wang, YinLan Zhao, Feng Luo, LiJuan Chen, Xia Zhao, YuQuan Wei & ZhiYong Qian

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  1. MaLing Gou
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  2. XiuLing Zheng
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  3. Ke Men
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  4. Juan Zhang
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  5. BiLan Wang
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  6. Lei Lv
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  9. Feng Luo
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  11. Xia Zhao
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  13. ZhiYong Qian
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Corresponding author

Correspondence to ZhiYong Qian.

Additional information

This work was financially supported by National Natural Science Foundation of China (NSFC20704027), National 863 project (2007AA021902, 2007AA021804 and 2006AA03Z356), Specialized Research Fund for the Doctoral Program of Higher Education (200806100065) and Chinese Key Basic Research Program (2004CB518807).

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Gou, M., Zheng, X., Men, K. et al. Self-Assembled Hydrophobic Honokiol Loaded MPEG-PCL Diblock Copolymer Micelles. Pharm Res 26, 2164–2173 (2009). https://doi.org/10.1007/s11095-009-9929-8

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  • DOI: https://doi.org/10.1007/s11095-009-9929-8

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