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Pegylated Phospholipids-Based Self-Assembly with Water-Soluble Drugs

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Abstract

Purpose

To investigate the self-assembly of polyethylene glycol (PEG)-phosphatidylethanolamine (PE) conjugate with water-soluble drugs (doxorubicin hydrochloride, vinorelbine tartrate and vincristine sulfate) and give insight into the mechanism of formation and mode of interaction of the drug with PEG-PE as well as the general principles of self-assembly using pegylated lipid micelles.

Methods

One-step self-assembly method to prepare drug-loaded micelles was developed. The micelles were characterized by dynamic light scattering, transmission electron microscopy, encapsulation efficiency, and release study. NMR was used to study molecular assembly of PEG-PE with doxorubicin.

Results

Doxorubicin hydrochloride and vinorelbine tartrate were entrapped into micelles with high efficiency of >99.0% at molar ratios of 1:1 and 2:1 of PEG-PE to drugs, respectively. Drug loading did not measurably perturb either the geometry or the size. It was found that electrostatic interaction and hydrophobic forces are responsible for the intercalation of drugs into PEG-PE micelles. NMR data revealed that the anthracycline ring of doxorubicin was inserted between PE phospholipids, and its amino sugar located in the outer shell of micelle between PEG chains.

Conclusion

Based on our results, the structure and self-assembly mechanism of water-soluble drugs encapsulated in PEG-PE micelles were proposed.

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Acknowledgements

This work was supported by grants from the National Nature Sciences Foundation of China (No. 90606019, 30901869), China Postdoctoral Science Foundation (No. 20090450598), State Key Development Plan Project (2006CB933305, 2007CB935801) and China-Finland Inter-Governmental S&T Cooperation Project (2008DFA01510).

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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

    Yiguang Wang, Ruiqi Wang, Xiaoyan Lu, Chunling Zhang & Wei Liang

  2. School of Pharmaceutical Sciences, Peking University, Beijing, 100083, China

    Wanliang Lu

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

    Wei Liang

Authors
  1. Yiguang Wang
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  2. Ruiqi Wang
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  3. Xiaoyan Lu
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  4. Wanliang Lu
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  5. Chunling Zhang
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  6. Wei Liang
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Correspondence to Chunling Zhang or Wei Liang.

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Wang, Y., Wang, R., Lu, X. et al. Pegylated Phospholipids-Based Self-Assembly with Water-Soluble Drugs. Pharm Res 27, 361–370 (2010). https://doi.org/10.1007/s11095-009-0029-6

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  • DOI: https://doi.org/10.1007/s11095-009-0029-6

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