| Project/Area Number |
26860031
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Physical pharmacy
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| Research Institution | Sojo University |
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Principal Investigator |
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| Project Period (FY) |
2014-04-01 – 2016-03-31
|
| Project Status |
Completed (Fiscal Year 2015)
|
| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | すい臓がん / ピラルビシン / 高分子ポリマー / HPMA / 高分子化抗がん剤 / 高分子抗がん剤 |
|---|
| Outline of Final Research Achievements |
Many conjugates of water-soluble polymers with biologically active molecules were developed. However, therapeutic effects of these conjugates do not depend only on the structures and properties of the polymer carriers; they are strongly influenced by properties and mechanisms of action of the attached drugs. Pirarubicin (THP), a tetrahydropyranyl derivative of doxorubicin (DOX), demonstrated more rapid cellular internalization and potent cytotoxicity than DOX. Here, we conjugated the THP or DOX to HPMA polymer via a hydrazone bond. The polymer prodrugs P-THP and P-DOX, respectively, had comparable hydrodynamic sizes and drug loading. Compared with P-DOX, P-THP showed approximately 10 times greater cellular uptake and a cytotoxicity. No significant difference occurred in the tumor drug concentration during 6-24 h after drug administration. Antitumor activity against xenograft human pancreatic tumor (SUIT2) in mice was greater for P-THP than for P-DOX.
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