Enhanced tumor Localization of anticancer drugs by synthetic marcomolecular carrier system
| Project/Area Number |
13672406
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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 |
応用薬理学・医療系薬学
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| Research Institution | Fukuyama University |
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Principal Investigator |
KANEO Yoshiharu Fukuyama University, Faculty of Pharmacy and Pharmaceutical Sciences, Professor, 薬学部, 教授 (70103075)
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| Co-Investigator(Kenkyū-buntansha) |
TANAKA Tetsuro Fukuyama University, Faculty of Pharmacy and Pharmaceutical Sciences, Associate Professor, 薬学部, 教授 (90163542)
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2002: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2001: ¥2,300,000 (Direct Cost: ¥2,300,000)
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| Keywords | synthetic polymer / poly (vinyl alcohol) / anticancer drug / daunorubicin / doxorubicin / tumor / macromolecular conjugate / EPR効果 |
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| Research Abstract |
In cancer chemotherapy, localizing such highly cytotoxic anticancer drugs to tumor tissues has been expected in order to minimize undesirable side effects. In this study we have examined the biodisposition of poly(vinyl alcohol) (PVA) as a synthetic macromolecular carrier system. Furthermore we covalently bound daunorubicin (DNR) and doxorubicin (DOX) to the PVA via an acid-labile cis-aconityl spacer. PVA was found to retain in the blood circulation for a long period having a low body distribution. PVA also showed a linear biodisposition over a wide range of concentration without depending on a dose. [^<125>I]PVA was predominantly accumulated in the tumor tissue after injection to S180 tumor bearing mice. Fluorescence microscopic examination also revealed that FITC-labeled PVA was effectively localized to the tumor tissue. The cis-aconityl linkage between the anticancer drugs and PVA was pH-sensitive with a hydrolysis in acidic media (pH 4-6). HPLC analysis indicated that the product of hydrolysis was unaltered drugs. Radiolabeled PVA conjugate of DOX was found to localize in the tumor tissue after injection to S180 tumor bearing mice. The conjugate showed a significant antitumor activity against S180 tumor cells inoculated to mice.
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Report
(3 results)
Research Products
(3 results)
