| Project/Area Number |
20K16428
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 50020:Tumor diagnostics and therapeutics-related
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| Research Institution | Toyo University |
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Principal Investigator |
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2022: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2021: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2020: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | Nano Drug Delivery / Ischemic Stroke / Neurotrophins / Blood Brain Barrier / Neurodegeneration / Nano DDS / Central Nervous System / Neuronal Degeneration |
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| Outline of Research at the Start |
NP-based platforms have attracted much attention for the delivery of drugs/molecules with neuroprotective/regenerative activities that, under normal conditions, cannot pass through the blood brain barrier (BBB).
Making neurotrophins a clinical reality for patients with neuronal degeneration and physical trauma (i.e., age-related/accidents/sports-related injuries) is of prime essence.
Therefore, the current research project aims to develop an efficient strategy employing highly biocompatible nanoparticles for delivering neutrophins across the BBB to the brain.
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| Outline of Final Research Achievements |
This project was designed to make neurotrophins, a clinical reality for patients with neuronal degeneration, particularly ischemic stroke. Specific peptide-targeted hybrid solid lipid nanoformulations (HSLNs) encapsulating neurotrophic factors with ability to trespass the blood brain barrier (BBB) and alleviate neuronal degeneration were utilized.
The HSLNs had excellent in vitro/vivo biocompatibility. Successful MCAO models were established for the study. HSLNs loaded with NGF &/or BDNF, either non-targeted or RDP/RMP-7 targeted were tested. For targeting investigations ICG dye was encapsulated instead of neurotrophins. RDP targeted HSLNs showed excellent results with increased accumulation, determined by in vivo/ex vivo imaging, in the ischemic region of the brain. This was reflected in the therapeutic investigations as well with majority of the ischemia induced-RDP/BDNF HSLN treated mice showing highly reduced ischemic zone. Overall, the research was a great success.
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| Academic Significance and Societal Importance of the Research Achievements |
本プロジェクトで開発したナノ製剤は、血液脳関門を効率的に通過し、疾患部位に神経保護剤を送達することにより、虚血性脳卒中によって引き起こされる神経変性を効果的に軽減できることを明らかにしている。特に近年急速に進む世界人口の高齢化を考慮すると、本研究結果で示した高レベルの治療効率の達成は、科学的および社会的の双方において重要な意義を有するとともに大きなインパクトをもたらすと考える。
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