Project/Area Number |
09672204
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Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Physical pharmacy
|
Research Institution | Faculty of Pharmaceutical Sciences, Kobe Gakuin University |
Principal Investigator |
YAMAOKA Yumiko (1998-1999) Kobe Gakuin Univ., Faculty of Pharmaceutical Sciences, Professor, 薬学部, 教授 (30102924)
市川 秀喜 (1997) 神戸学院大学, 薬学部, 助手 (00248105)
|
Co-Investigator(Kenkyū-buntansha) |
FUKUMORI Yoshinobu Kobe Gakuin Univ., Fac. Of Pharm. Sci., Professor, 薬学部, 教授 (60102927)
山岡 由美子 神戸学院大学, 薬学部, 助教授 (30102924)
|
Project Period (FY) |
1997 – 1999
|
Project Status |
Completed (Fiscal Year 1999)
|
Budget Amount *help |
¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 1999: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1998: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1997: ¥1,600,000 (Direct Cost: ¥1,600,000)
|
Keywords | Cancer therapy / Chemo-embolization / Microcapsule / Lecithin / controlled-release / Adriamycin / Coating / Fluidized bed / 癌治療 / 生体内崩壊性 / 多機能性微粒子 |
Research Abstract |
Lecithin microcapsules (LMCs) specified by short-term delayed drug-release and bioerosion were developed for intraarteial chemoembolization therapy of cancer. An air suspension coating process was employed to microencapsulate a lactose core with a layer of drug, soybean lecithin (SL), cholesterol (CH), stearic acid (SA) and polyvinylpyrrolidone (PVP) and a coat of SL, CH, SA and PVP. The particle size drug content of the LMCs thus prepared could be varied in the range of 30-200 μm and few to 30%, respectively. By changing the weight rations of four components of the LMCs coat, bioerosion and short-term drug-release properties were also found to be widely changeable. The estimated phase diagram of the SL-CH-SA system incorporating 42% PVP indicated that the mechanisms of drug-release and bioerosion were closely related to the phase-separation behavior of each component in the coat. Small-scale production of the LMCs by the air suspension coating process was also established based on a novel dilution method, taking into consideration of the tailor-made treatment for individual patients in preclinical use where various types of microcapsules with versatile functions were required. This method provided microcapsules with 106-149 μm in size and 30% in drug content by using only 1 g of an anticancer drug (adriamycin (ADR)). The ADR-containing LMCs also demonstrated short-term delayed release of ADR with a lagtime of few to ten minutes while they could be completely eroded within 30 min in human plasma in vitro. These properties were achieved even in vivo studies where the ADR-LMCs were intraarterially injected to hepatic artery of rats, suggesting that the ADR-LMCs may induce transient arterial-embolization and thereby enhance the pharmacological effect of ADR released in the embolic arteries. These results demonstrate that the LMCs developed in this study will be a promising class of drug carriers for intraarterial chemoembolization therapy of cancer.
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