Therapeutic effcacy 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, Teiji Tominaga

Research output: Contribution to journalArticlepeer-review

51 Citations (Scopus)

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 effcacy 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 5 0.0173) and liposomal DOX (16.6 days; p 5 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. Neuro-Oncology 11, 151-157, 2009 (Posted to Neuro- Oncology [serial online], Doc. D08-00039, August 28, 2008. URL http://neuro-oncology.dukejournals.org;

Original languageEnglish
Pages (from-to)151-157
Number of pages7
JournalNeuro-Oncology
Volume11
Issue number2
DOIs
Publication statusPublished - Apr 2009
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Oncology
  • Clinical Neurology
  • Cancer Research

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