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Convection-enhanced delivery of liposomal doxorubicin in intracranial brain tumor xenografts

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Abstract

We previously reported that convection-enhanced delivery (CED) of liposomes into brain tissue and intracranial brain tumor xenografts produced robust tissue distribution that can be detected by magnetic resonance imaging. Considering image-guided CED of therapeutic liposomes as a promising strategy for the treatment of brain tumors, we evaluated the efficacy of pegylated liposomal doxorubicin delivered by CED in an animal model. Distribution, toxicity, and efficacy of pegylated liposomal doxorubicin after CED were evaluated in a U251MG human glioblastoma intracranial xenograft model. CED of pegylated liposomal doxorubicin achieved good distribution in brain tumor tissue and surrounding normal brain tissue. Distribution was not affected by the particle concentration of pegylated liposomal doxorubicin, but tissue toxicity increased at higher concentrations. CED of pegylated liposomal doxorubicin, at a dose not toxic to normal rat brain (0.1 mg/ml doxorubicin), was significantly more efficacious than systemic administration of pegylated liposomal doxorubicin at the maximum tolerated dose. CED of pegylated liposomal doxorubicin resulted in improved survival compared to CED of free doxorubicin at the same dose. Outcomes of this study suggest that CED of liposomal drugs is a promising approach for the treatment of glioblastoma.

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Acknowledgements

Special thanks John Forsayeth Ph.D. for proofreading and editing this work. Grant support: National Cancer Institute Specialized Program of Research Excellence grant (to M. S. Berger, K. S. Bankiewicz, and J. W. Park) and Accelerate Brain Cancer Cure (to K. S. Bankiewicz).

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Authors and Affiliations

  1. Department of Neurological Surgery, University of California, San Francisco, 1855 Folsom Street, Mission Center Building, Room 226, San Francisco, CA, 94103, USA

    Yoji Yamashita, Ryuta Saito, Michal T. Krauze, Tomohiro Kawaguchi, Mitchel S. Berger & Krystof S. Bankiewicz

  2. Division of Hematology–Oncology, University of California, San Francisco, San Francisco, CA, USA

    Charles Noble & John W. Park

  3. Hermes Biosciences, Inc., South San Francisco, CA, USA

    Daryl C. Drummond, Dmitri B. Kirpotin & John W. Park

Authors
  1. Yoji Yamashita
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  2. Ryuta Saito
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  3. Michal T. Krauze
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  4. Tomohiro Kawaguchi
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  5. Charles Noble
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  6. Daryl C. Drummond
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  7. Dmitri B. Kirpotin
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  8. John W. Park
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  9. Mitchel S. Berger
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  10. Krystof S. Bankiewicz
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Correspondence to Krystof S. Bankiewicz.

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Yamashita, Y., Saito, R., Krauze, M.T. et al. Convection-enhanced delivery of liposomal doxorubicin in intracranial brain tumor xenografts. Targ Oncol 1, 79–85 (2006). https://doi.org/10.1007/s11523-006-0011-8

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  • DOI: https://doi.org/10.1007/s11523-006-0011-8

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