2006 Fiscal Year Final Research Report Summary
Development of targeting therapy using versatile nanotransporter
| Project/Area Number |
17591346
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General surgery
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| Research Institution | KEIO UNIVERSITY |
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Principal Investigator |
JINNO Hiromitsu Keio University, School of Medicine, Associate Professor, 医学部, 講師 (20216261)
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| Co-Investigator(Kenkyū-buntansha) |
KANKE Daisuke Keio University, School of Medicine, Assistant Professor, 医学部, 助手 (00365272)
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| Project Period (FY) |
2005 – 2006
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| Keywords | breast cancer / targeting therepy / MPC polymer / paclitaxel |
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| Research Abstract |
<Background・Purpose>Paclitaxel (PTX) needs a special solvent such as Cremophor EL because of its low solubility in water, requiring complicated premedication treatment and prolonged intravenous drip in order to prevent side effects caused by Cremophor EL. And Injection site reactions, including reactions secondary to extravasation, were usually severe. MPC polymer (PMB30W) is a novel water-soluble phospholipid polymer that could dissolve PTX more than 1000 times than water, and also shows excellent biocompatibility because of its side chain with a phospholipid polar group. In the present study, we report the anti-tumor effects and the reactions of subcutaneous injection of PTX examined in vivo. <Methods>The anti-tumor effects of PXT dissolved in PMB30W and PXT dissolved in Cremophor EL by intra-peritoneal administration were compared by using nude mice transplanted with human MX-1 breast cancer cells. The administration schedules for both groups were identical and were 2 cycles of week
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ly intra-peritoneal administration of dose of 200 mg/kg of PTX and 50mg/kg of PTX. <Results>No significant difference in the anti-tumor effect was found between the PXT-PMB3OW and PXT-Cremophor EL groups (p=0.61) at the dose of 50mg/kg of PXT on Day 16. At the dose of 200 mg/kg of PTX, all animals died within 1 minute of administration in the PXT-Cremophor EL group, while all animals in the PXT-PBM30W group not only survived but showed better inhibitory effect of tumor growth than in the both groups of Cremophor EL group and PBM30W administration at dose of 50mg/kg of PTX (p<0.01). The Subcutaneous injection of PTX-PMB30W did not cause any macroscopical and microscopical change of the skin. <Conclusion>The use of PTX-PMB30W has made it possible to treat with PXT dose that is higher than with PTX-Cremophor EL. Also, the anti-tumor effect was found to be concentration-dependent. PTX-PMB30W could have the potential of not only the anti-tumor effect but also the safety concerned with the extravasation. Less
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