| Project/Area Number |
05455022
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
広領域
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| Research Institution | Science University of Tokyo |
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Principal Investigator |
KATAOKA Kazunoei Science University of Tokyo, Department of Materials Science and Technology, Professor, 基礎工学部, 教授 (00130245)
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| Co-Investigator(Kenkyū-buntansha) |
SAKURAI Yasuhisa Tokyo Women's Medical College, Institute of Biomedical Engineering, Professor, 医用工学研究施設, 教授 (20010027)
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| Project Period (FY) |
1993 – 1994
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| Project Status |
Completed (Fiscal Year 1994)
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| Budget Amount *help |
¥4,200,000 (Direct Cost: ¥4,200,000)
Fiscal Year 1994: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1993: ¥3,500,000 (Direct Cost: ¥3,500,000)
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| Keywords | poly (ethylene glycol) / poly (aspartic acid) / block copolymer / adriamycin / polymeric micelle / heterobifunctional oligomer / pharmacokinetics / solid tumor / ヘテロニ官能性オリゴマー / 薬物ターゲティング / 制ガン剤 |
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| Research Abstract |
The polymeric micelles have an important place in the field of drug delivery systems. Indeed, such carriers can be considered to bo close to natural carriers such as viruses because of their small size, apparent stability and capacity for drug solubilization. The polymeric micelles formed by alpha-methoxy PEO/PBLA blck-copolymers already gave interesting results (small diameter, c.a.20nm ; stability ; possibility of anti-cancer drug solubilization, Adriamycin for example). Besides the fact of decreasing the side effects of anti-cancer drugs by entrapment in a carrier, the preparation of intelligent materials which are able to recognize selectively their objective is of interest. For this purpose, the synthesis of micelles having functional groups (such as hydroxy groups) on their outer-shell is necessary. In this project, we conducted the synthesis of heterobifunctional PEO/PBLA block-copolymers as well as the synthesis and chariacterzation of the resulting polymeric micelles.
The stabi
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lity of polymeric micelles in blood is strongly correlated with their enhanced accumulation in tumors. Tumor accumulation ratios to normal tissue (muscle) at 24 hours for polymeric micelles (tumor/muscle ratio=40) showed an order of magnitude increase in comparison to free adriamycin (tumor/muscle ratio=1.5). An increase in the tumor accumulation ratio to the heart was also significant for the micelle-forming conjugate, suggesting a low incidence of cardiac toxicity in the conjugate system. Accumulation of the conjugate at tumor sites, possibly throughdirect extravasation, might be due to enhanced vascular permeability and retention effects in a tumor, known as the EPR effect. To achieve this effect at a sufficient level, it will be important to emphasize the core-shell structure of the micelle in order to inhibit nonspecific intertactions of the hydrophobic core of the micelle with the biocomponents (e.g., RES) by covering the core with a hydrated outer shell which will provide higher stability of the micelle structure in blood. Less
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