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

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.
Authors	Tomoo Inoue, Yoji Yamashita, Masamichi Nishihara, Shinichiro Sugiyama, Yukihiko Sonoda, Toshihiro Kumabe, Masayuki Yokoyama, Teiji Tominaga
Journal	Neuro-oncology (Neuro Oncol) Vol. 11 Issue 2 Pg. 151-7 (Apr 2009) ISSN: 1522-8517 [Print] England
PMID	18755917 (Publication Type: Journal Article)
Chemical References	Antibiotics, Antineoplastic Drug Carriers Liposomes Micelles Polymers Doxorubicin
Topics	Animals Antibiotics, Antineoplastic (administration & dosage, pharmacokinetics) Brain Neoplasms (drug therapy, metabolism) Cell Line, Tumor Convection Disease Models, Animal Doxorubicin (administration & dosage, pharmacokinetics) Drug Carriers (therapeutic use) Drug Delivery Systems Gliosarcoma (drug therapy, metabolism) Liposomes Male Micelles Polymers (chemistry) Rats Rats, Inbred F344 Rats, Sprague-Dawley Survival Rate Tissue Distribution Treatment Outcome Xenograft Model Antitumor Assays

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