| Project/Area Number |
20K20194
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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 90120:Biomaterials-related
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| Research Institution | University of Tsukuba |
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Principal Investigator |
SHASHNI BABITA 筑波大学, 数理物質系, 特任助教 (90869629)
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| Project Period (FY) |
2020-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2021: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2020: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | Short-chain fatty acid / Polymeric micelle / Self assembling / Controlled release / Cancer / Obesity / Non-alcoholic hepatitis / Diabetes / SCFA nanoparticle / Radiation therapy / Pharmacokinetic / Bioavailability / cancer / radio-sensitizer / radiation therapy / NASH / controlled release / Short chain fatty acid / nano-micelle / Anti-cancer / Anti-obesity / Radio-sensitizer |
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| Outline of Research at the Start |
Low molecular weight short chain fatty acids possesses low in vivo efficacy due to their rapid metabolism and their adverse effects. Hence, to overcome this limitation, we designed self-assembling metabolizable SCFA block copolymer to evaluate therapeutic efficacy in cancer and obesity model.
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| Outline of Final Research Achievements |
We successfully synthesized base polymer PEG-b-PVRs (R=propionic, butyric acid) and prepared stable nano-sized short-chain fatty acid nanoparticles (SCFA) (PNP and BNP). We confirmed anti-cancer effect of PNP and BNP in a B16F10 metastasis melanoma model. We also confirmed that by single administration of BNP 24 h prior to irradiation, sensitizes B16F10 subcutaneous tumors in mouse model for the radiation therapy, whereas low molecular weight (LMW) butyric acid had no effect at lower dose. We also confirmed improvement in disease symptoms in in high fat diet-induced obesity and non-alcoholic hepatitis model. Similarly, in diabetic db/db mice, we confirmed that BNP (free drinking) and the conventional exenatide (intraperitoneal) improved the diabetic symptoms such as glucose utilization as compared to LMW SCFA groups. We also observed that by intraperitoneal route, butyric acid released by BNP has higher bioavailability than LMW butyric acid, confirmed by in vivo imaging and LCMS/MS.
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| Academic Significance and Societal Importance of the Research Achievements |
Clinical application of short-chain fatty acids (SCFA) is limited due to their poor pharmacokinetics. Here, we succeeded in improving their pharmacokinetic properties by delivering them as a prodrug nanoparticle, resulting in a higher therapeutic effect in the several disease.
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