| Co-Investigator(Kenkyū-buntansha) |
HIRATSUKA Junichi Kawasaki Medical School, Department of Radiation Oncology, Lecturer, 医学部, 講師 (30192298)
ICHIKAWA Hideki Kobe Gakuin University, Faculty of Pharmaceutical Sciences, Research Assistant, 薬学部, 助手 (00248105)
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| Research Abstract |
1) Synthesis of hydrophobic chelates
Stearylamide (SAm) and stearyl ester (SE) of diethylenetriaininepentaacetic acid (DTPA) could be synthesized in a large scale.
2) Lecithin microcapsules(MC)
Based on the phase diagrams of soybean lecithin (SL)-cholesterol (CH)-stearic acid (SA)-PVP system in dry and hydrated states, a swelling type (the weight ratio of SL, CH, SA and PVP, 5 : 5 : 2 : 5), a erosion type(12 : 0 : 0 : 5) and a self-dispersion type (5 : 5 : 0 : 5) of microcapsules containing Gd-DTPA-SAm were prepared by a spouted bed process. It was biochemically, histologically confirmed that their intraarterial injection to rat liver induced only a temporary damage to the liver. The prepared microcapsules also retained 70% of injected gadolinium in the rat liver.
3) Emulsions
A preparation method of nanoemulsions was established using Gd-DTPA-SAm, hydrogenated phosphatidyicholine, soybean oil and such a cosurfactant as Tween80, Myrj53 and HCO6O.Biodistribution of Gd was investigated by int
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raperitoneally injecting the emulsion in D1-179 (melanotic)-bearing hamster. The Gd concentration in tumor at 24 hours after injection was the highest with the HCO6O emulsion, 62.6 , mugGd/g-wet tissue. The HCO6O emulsion formulated so as to contain twofold Gd exhibited an effective level of 107 mugGd/g-wet tissue in tumor 48 hours after injection ; then, the tumor-blood concentration ratio was 13.7.
4) Particulate systems for depot of gadolinium
A novel emulsion-droplet coalescence technique for preparing highly Gd-DTPA-loaded chitosan micro-and nano -particles (nanoCP) was established. The Gd content in nanoCPs of 452 nm reached 13%. By neutron irradiation on B16F1O melanoma-bearing mice after intratumorally injecting the nanoCPs, tumor growth was remarkably suppressed. Further, dose dependency of tumor growth suppression was investigated by intratumorally injecting them in SCC-VII tumor-bearing mice. The suppression was dose-dependently increased with dose until 600 mugGd/g-body weight and leveled above that. This was the first study which quantitatively made the effective dose clear in vivo for gadolinium neutron-capture therapy. Less
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