| Project/Area Number |
22800004
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| Research Category |
Grant-in-Aid for Research Activity Start-up
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| Allocation Type | Single-year Grants |
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| Research Field |
Biomedical engineering/Biological material science
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| Research Institution | University of Tsukuba |
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Principal Investigator |
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| Project Period (FY) |
2010 – 2011
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| Project Status |
Completed (Fiscal Year 2011)
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| Budget Amount *help |
¥3,146,000 (Direct Cost: ¥2,420,000、Indirect Cost: ¥726,000)
Fiscal Year 2011: ¥1,508,000 (Direct Cost: ¥1,160,000、Indirect Cost: ¥348,000)
Fiscal Year 2010: ¥1,638,000 (Direct Cost: ¥1,260,000、Indirect Cost: ¥378,000)
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| Keywords | 酸化ストレス障害 / ドラックデリバリーシステム / 高分子ミセル |
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| Research Abstract |
We have developed pH-sensitive nitroxide radical-containing nanoparticles (RNP^N) prepared by a self-assembling amphiphilic block copolymers (PEG-b-PMNT ; poly(ethylene glycol)-b-poly[4-(2,2,6,6-tetramethylpiperidine-1-oxyl)aminomethylstyrene]). This self-assembled RNP^N disintegrates at pH below 7.0 because of a protonation of amino groups in the hydrophobic segment of the PEG-b-PMNT, thereby resulting in an improvement in ROS scavenging activity. Using a renal ischemia-reperfusion induced acute kidney injury model in mice, the protective effect of RNP^N was evaluated. The formation of polymeric micelle in bloodstream and disintegration of RNP^N in injured kidney area were confirmed by electron spin resonance spectra. Due to these characters, the RNP^N showed extremely high ROS scavenging activity and renal protective effect, compared to low molecular weight nitoroxide radical derivatives. It is interesting to note that the side effect of nitroxide radicals was markedly suppressed due to the compartmentalization of nitroxide radicals in the core of RNP^N in untargeted area. On the basis of these results, this system is expected as a new medication for therapy of various oxidative stress injuries.
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