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First published on August 28, 2008
A more recent version of this article appeared on January 1, 2009
Neuro Oncol 2008, DOI:10.1215/15228517-2008-068
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© Copyright 2008 by the Society for Neuro-Oncology

Received February 18, 2008
Accepted July 7, 2008

Basic and Translational Investigations

Therapeutic efficacy of a polymeric micellar doxorubicin infused by convection-enhanced delivery against intracranial 9L brain tumor models

Tomoo Inoue 1, Yoji Yamashita 1*, Masamichi Nishihara 2, Shinichiro Sugiyama 1, Yukihiko Sonoda 1, Toshihiro Kumabe 1, Masayuki Yokoyama 2, Teiji Tominaga 1

1 Department of Neurosurgery, Tohoku University Graduate School of Medicine, Sendai, Japan
2 Yokoyama Nano-medical Polymers Project, Kanagawa Academy of Science and Technology, Kawasaki, Japan

* To whom correspondence should be addressed. E-mail: yoji{at}nsg.med.tohoku.ac.jp.


  Abstract

Purpose: Convection-enhanced delivery (CED) with various drug carrier systems has recently emerged as a novel chemotherapeutic method to overcome the problems of current chemotherapies against brain tumors. Polymeric micelle systems have exhibited dramatically higher in vivo antitumor activity in systemic administration. This study investigated the effectiveness of CED with polymeric micellar doxorubicin (micellar DOX) in a 9L syngeneic rat model.

Experimental Design: Distribution, toxicity, and efficacy of free, liposomal, and micellar DOX infused by CED were evaluated.

Results: Micellar DOX achieved much wider distribution in brain tumor tissue and surrounding normal brain tissue compared to free DOX. Tissue toxicity increased at higher doses, but rats treated with micellar DOX showed no abnormal neurological symptoms at any dose tested (0.1-1.0 mg/mL). Micellar DOX infused by CED resulted in prolonged median survival (36 days) compared to free DOX (19.6 days; P=0.0173) and liposomal DOX (16.6 days; P=0.0007) at the same dose (0.2 mg/mL).

Conclusions: This study indicates the potential of CED with the polymeric micelle drug carrier system for the treatment of brain tumors.

Key Words: brain tumors, d convection-enhanced delivery, oxorubicin, drug delivery system, polymeric micelle


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Copyright 2008 by Society for Neuro-Oncology