| Project/Area Number |
18591578
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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, the Graduate School of Medicine, Project Assistant Professor (50372371)
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| Co-Investigator(Kenkyū-buntansha) |
TODO Tomoki The University of Tokyo, Hospital Department of Neurosurgery, Assistant Professor (80272566)
KATAOKA Kazunori The University of Tokyo, the Graduate School of Engineering, Professor (00130245)
NISHIYAMA Nobuhiro The University of Tokyo, Faculty of Medicine, Assistant Professor (10372385)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥4,010,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥510,000)
Fiscal Year 2007: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2006: ¥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 / ナノミセル / ドラッグ・デリバリー・システム |
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| Research Abstract |
Polymeric micelle is one of new modalities of macromolecular drug carrier systems. This method can (1) increase water solubility of otherwise highly hydrophobic drug, and (2) decrease the toxicity of the drug until delivered and released at the target site. Dichloro (1, 2-diaminocyclohexane) platinum(II) (DACHPt) is a platinum-based anticancer drug. We have developed a polymeric micelle incorporating DACHPt (DACHPt/m). The core drug stays inactive until slowly released via ligand exchange with surrounding chloride ions. The efficacy of DACHPt/m was tested in A/J mice harboring Neuro2a (murine neuroblastoma) subcutaneous or intracerebral tumors, and compared with oxaliplatin, a less toxic derivative of DACHPt. Although DACHPt/m was significantly more effective in inhibiting the growth of Neuro2a subcutaneous tumors than oxaliplatin at maximum tolerated dose (MTD), there remained considerable systemic toxicity in this passive controlled release system. pH responsive controlled release adriamycin (ADR) micelle(ADR/m) was also designed. ADR/m becomes active only when exposed to lower pH in tumor cell cytoplasm. When tested in U87MG subcutaneous tumor model in nude mice, ADR/m was significantly more efficacious in inhibiting tumor growth than free ADR while maintaining reduced systemic toxicity. Whether the micelle can reach intracranial tumors across the blood brain barrier is yet to be examined, these results still suggest that the polymeric micelle drug delivery system can be useful for improving the efficacy of chemotherapy for brain tumors.
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