|Budget Amount *help
¥12,800,000 (Direct Cost : ¥12,800,000)
Fiscal Year 2004 : ¥2,000,000 (Direct Cost : ¥2,000,000)
Fiscal Year 2003 : ¥2,000,000 (Direct Cost : ¥2,000,000)
Fiscal Year 2002 : ¥8,800,000 (Direct Cost : ¥8,800,000)
In this study, we intended to investigate how much gadolinium, a sensitizer in neutron capture therapy (NCT) of cancer, could be accumulated in tumor by using Gd-containing nanoparticles. The nanoparticles were designed and prepared so as to utilize the enhanced penetration and retention effect.
The results obtained through this project are summarized as follows :
1.The chitosan nanoparticles (nanoCP) could strongly hold gadopentetic acid which had an extremely high water-solubility. The chitosan nanoparticles of 155 nm in mean size could be prepared by using a chitosan of low molecular weight, 10 kDa, in the slightly modified emulsion droplet coalescence method, with such a high Gd-content as 23%. They efficiently associated to B16F10 melanoma cells, leading to strong cell-killing effect in neutron irradiation study in vitro.
2.A suspension of Gd-containing micellar lipid nanoparticles (Gd-nanoMIC) was designed and prepared with a mean diameter of 38 nm and a Gd concentration of 4.5 mg/m
L. After intravenous administration of its 2 ml by continuous injection, Gd concentration reached 164 ppm, which was significantly higher than that in the case of twice repeated injection of 1 mL each and higher than the minimum effective level previously estimated in Gd-NCT in vivo.
The following technical information and developments which should be beneficial in the future studies of NCT were obtained.
1.The typical boron compounds, BPA and BSH, used in clinical treatment could not be hold in the nanoLE, nanoMIC and nanoCP at a sufficient content. In order to apply the nanoparticulate systems developed in this study to BNCT, the highly boron-containing BSH was suggested to be synthesized in a large scale and, by using it, a systematic chemical-modification study has to be started.
2.Through this study, an efficient preparation method, the emulsion precipitation method, of chitosan nanoparticles, an preparation method of poly(epsiron-caprolactone) nanoparticles and a new dry, sanitary and small-scale process of nanoparticles were developed. They will be useful in the future works on developing new nano and micro-devices for NCT. Less