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Stability Influences the Biodistribution, Toxicity, and Anti-tumor Activity of Doxorubicin Encapsulated in PEG-PE Micelles in Mice

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ABSTRACT

Purpose

To investigate the influences of stability of doxorubicin (DOX) retained in PEG-PE/HSPC micelles on its biodistribution, toxicity and anti-tumor activity in mice.

Methods

We incorporated HSPC into PEG-PE micelles at various molar ratios by a self-assembly procedure. Micelles were characterized by dynamic light scattering, transmission electron microscope, atomic force microscopy. Agarose gel electrophoresis assay was used to detect stable retention of DOX in micellar preparations. Biodistribution, toxicity and anti-tumor activity of doxorubicin encapsulated in PEG-PE/HSPC micelles in mice were investigated.

Results

HSPC incorporation not only changed the size and shape of PEG-PE micelles, but also decreased the ability of DOX stable retained in PEG-PE micelles, resulting in a great discrepancy in biodistribution, toxicity and anti-tumor activity among micellar DOX preparations. DOX encapsulated in PEG-PE micelles (M1-DOX), with narrower size distribution and greater stability, demonstrated better cytotoxicity in vitro and low systemic toxicity with superior anti-tumor metastasis activity in vivo.

Conclusions

Encapsulation of DOX into PEG-PE micelles showed the best therapeutic activity and lowest systemic toxicity compared to other HSPC-incorporated PEG-PE micellar preparations. Stable retention of drugs within micelles is important and is determined by compatibility between drugs and polymer blocks.

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ACKNOWLEDGMENTS & DISCLOSURES

This work was supported by grants from State Key Development Plan Project (2007CB935801), the National Nature Sciences Foundation of China (30901869).

Dr Junfeng Hao of the IBP core facilities centre was gratefully thanked for her help for Histopathology and TUNEL assay.

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Authors and Affiliations

  1. Protein & Peptide Pharmaceutical Laboratory National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China

    Xiuli Wei, Yiguang Wang, Wenfeng Zeng, Feng Huang, Lei Qin, Chunling Zhang & Wei Liang

  2. National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, 15 Datun Road, Beijing, 100101, China

    Chunling Zhang & Wei Liang

Authors
  1. Xiuli Wei
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  2. Yiguang Wang
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  3. Wenfeng Zeng
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  4. Feng Huang
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  5. Lei Qin
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  6. Chunling Zhang
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  7. Wei Liang
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Corresponding authors

Correspondence to Chunling Zhang or Wei Liang.

Additional information

Xiuli Wei and Yiguang Wang contributed equally to this work.

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Wei, X., Wang, Y., Zeng, W. et al. Stability Influences the Biodistribution, Toxicity, and Anti-tumor Activity of Doxorubicin Encapsulated in PEG-PE Micelles in Mice. Pharm Res 29, 1977–1989 (2012). https://doi.org/10.1007/s11095-012-0725-5

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  • DOI: https://doi.org/10.1007/s11095-012-0725-5

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