| Project/Area Number |
16591432
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Cerebral neurosurgery
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| Research Institution | The University of Tokyo |
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Principal Investigator |
INO Yasushi The University of Tokyo, Faculty of Medicine, Project Assistant Professor, 医学部附属病院, 研究拠点形成特任教員 (50372371)
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| Co-Investigator(Kenkyū-buntansha) |
TODO Tomoki The University of Tokyo, Faculty of Medicine, Lecturer, 医学部附属病院, 講師 (80272566)
KATAOKA Kazunori The University of Tokyo, the Graduate School of Engineering, Professor, 大学院・工学系研究科, 教授 (00130245)
NISHIYAMA Nobuhiro The University of Tokyo, Faculty of Medicine, Research Associate, 医学部附属病院, 助手 (10372385)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2005: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2004: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | Cancer / Central Nervous System / Drug Delivery / nano material / biomedical material / 悪性脳腫瘍 / 化学療法 / ドラッグ・デリバリー・システム / ナノミセル |
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| Research Abstract |
The use of polymeric micelles is one of the promising modalities of macromolecular carrier systems. Dichloro (1,2-diaminocyclohexane)platinum(II) (DACHPt) is a second-generation platinum based anticancer drug which is highly hydrophobic and is toxic when administered systemically. We have developed a polymeric micelle incorporating DACHPt (DACHPt/m) via the polymer-metal complex formation between DACHPt and poly(ethylene glycol)-poly(glutamic acid) block copolymers [PEG-P(Glc)]. In vivo antitumor effect of DACHPt/m was tested in Neuro2a (murine neuroblastoma) subcutaneous and intracerebral tumor models. Oxaliplatin, a less toxic derivative of DACHPt, was also used as a control. The maximum tolerated dose (MTD) of DACHPt/m in A/J mice was 1.75mg/kg and similar to that of oxaliplatin when administered from the tail vein three times every other day. Nonetheless, DACHPt/m was more effective in inhibiting the Neuro2a subcutaneous tumor growth than oxaliplatin at theed MTD level. Dach-Pt/m was also effective in the Neuro2a intracerebral tumor model and prolonged the survival of tumor-baring mice compared with oxaliplatin. Accumulation of DACHPt/m was 9.5 and 1.7 times higher in subcutaneous and intracerebral tumors, respectively, than that of oxaliplatin 48 hours after drug administration. These results suggest that the polymeric micelle system can be a useful macromolecular drug carrier for the treatment of brain tumors.
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