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Neuro-Oncology 2009 11(2):151-157; doi:10.1215/15228517-2008-068
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Copyright 2009 by the Society for Neuro-Oncology

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

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

Department of Neurosurgery, Tohoku University Graduate School of Medicine, Sendai (T.I., Y.Y., S.S., Y.S., T.K., T.T.), and Yokoyama Nano-medical Polymers Project, Kanagawa Academy of Science and Technology, Kawasaki (M.N., M.Y.); Japan

Address correspondence to Yoji Yamashita, Department of Neurosurgery, Tohoku University Graduate School of Medicine, 1-1, Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan (yoji{at}nsg.med.tohoku.ac.jp).


  Abstract

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 (DOX) in a 9L syngeneic rat model. Distribution, toxicity, and efficacy of free, liposomal, and micellar DOX infused by CED were evaluated. Micellar DOX achieved much wider distribution in brain tumor tissue and surrounding normal brain tissue than 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 with 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). This study indicates the potential of CED with the polymeric micelle drug carrier system for the treatment of brain tumors.

Keywords: brain tumors, convection-enhanced delivery, doxorubicin, drug delivery system, polymeric micelle

Received February 18, 2008; Accepted July 22, 2008


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