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.
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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)
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Chemical References |
- Antibiotics, Antineoplastic
- Drug Carriers
- Liposomes
- Micelles
- Polymers
- Doxorubicin
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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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