| Project/Area Number |
11470479
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Physical pharmacy
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| Research Institution | Kobe Gakuin University |
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Principal Investigator |
FUKUMORI Yoshinobu Kobe Gakuin University, Faculty of Pharmaceutical Sciences, Assistant Professor, 薬学部, 教授 (60102927)
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| Co-Investigator(Kenkyū-buntansha) |
ICHIKAWA Hideki Kobe Gakuin University, Faculty of Pharmaceutical Sciences, Assistant Professor, 薬学部, 講師 (00248105)
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| Project Period (FY) |
1999 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥11,400,000 (Direct Cost: ¥11,400,000)
Fiscal Year 2001: ¥2,600,000 (Direct Cost: ¥2,600,000)
Fiscal Year 2000: ¥5,100,000 (Direct Cost: ¥5,100,000)
Fiscal Year 1999: ¥3,700,000 (Direct Cost: ¥3,700,000)
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| Keywords | Gadolinium / Neutron-capture therapy / Cancer therapy / Drug delivery system / Chitosan / Emulsion / Nanoparticle / Biodistribution of drug |
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| Research Abstract |
This study intended to investigate how much sensitizer could be accumulated in tumor without using any materials that would have a specified affinity to tumor cells. It has been because we do not need active compounds such as anticancer drugs and can administer inactive compounds at a large dose in the neutron-capture therapy (NCT). Such an approach was also thought to be efficient for prompt clinical application of research results. The results obtained through this project are summerized as follows : 1. The chitosan nanoparticles (nanoCP) could strongly hold gadopentetic acid which had an extremely high water-solubility, but no specified affinity to tumor cells. Gd-nanoCPs could work as a carrier of Gd in the incorporation to tumor cells, leading to the tumor growth suppression observed in the previous trials of GdNCT. It was also suggested that endocytic activity of the cells might be related to the observed incorporation of Gd to the tumor cells, resulting in variation of incorporation among the types of cell. 2. The lipid nanoemulsion (nanoLE) exhibited the same level of Gd tumor-accumulation after intravenous injection as that after intraperitoneal injection. Different from liposomes, this emulsion could be formulated to be highly Gd-enriched with the particle size being kept smaller than 100 nm. The Gd tumor-accumulation reached 189 ppm by twice injections of his newly developed emulsion. This tumor level of Gd was expected to significantly suppress the tumor growth in vivo, when Gd-157 would be used. 3. The size reduction of nanoCP to smaller than 100 nm was tried, because nanoCP was thought to be an alternative of injectable paniculate systems. Instead of the emulsion droplet coalescence method developed for the original nanoCP, a new emulsion precipitation method was found to produce nanoparticles of 350 nm which was smaller than 450 nm of the original, though it was still too large.
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