| 研究実績の概要 |
We confirmed the radio-sensitizing effect of short chain fatty acid (SCFA) nanoparticle at lower doses (100 and 200 mg/kg) in B16F10 melanoma bearing mice. Butyric acid nanoparticle (NanoBA) 200 mg/kg showed the most suitable effect than low molecular weight (LMW) butyric acid. Mechanistic studies by western blotting and immuno-staining confirmed that DNA repair protein Ku70 and cyclooxygenase-2 (COX-2) were down regulated in NanoBA-treated group. In addition, proliferation marker Ki67 was also decreases in NanoBA-treated irradiation group as compared to the control. In diabetic db/db mice, we confirmed that NanoBA (free drinking) and the conventional exenatide (intraperitoneal: i.p.) improved the diabetic symptoms such as glucose utilization as compared to LMW SCFA groups. We conducted pharmacokinetic studies by oral and i.p. route. By oral route, our nanoparticles increased the bioavailability of butyric acid for 2 days, whereas butyric acid cleared from the blood in 6 h. We checked Pk parameters via i.p. route in a tumor bearing mice. We confirmed that butyric acid is cleared from the blood within 10 min whereas in NanoBA-treated group butyric acid is present until 24 h. We also observed the accumulation of nanoparticles in the tumor by in vivo imaging and western blotting. A sustained release of butyric acid was also observed significantly higher in tumors as compared to LMW SCFA. These results imply that our nanoparticles succeeded in improving the pharmacokinetic properties of LMW SCFA, which ultimately contributed to enhanced efficacy in various disease models.
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