1997 Fiscal Year Final Research Report Summary
Targetting therapy with liposome encapsulatedanticancerdrugin osteosarcoma on hamsters
| Project/Area Number |
08671663
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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 |
Orthopaedic surgery
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| Research Institution | HIROSHIM UNIVERSITY |
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Principal Investigator |
SUGITA Takashi Hiroshima University School of Medicine Associate Professor, 医学部, 助教授 (40235883)
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| Project Period (FY) |
1996 – 1997
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| Keywords | Muramyl dipeptide / Osteosarcoma / Liposomes / Hamsters / Thermosensitive / Doxorubicin / Localized hyperthermia / Controled release |
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| Research Abstract |
1. Our previous experiments have demonstrated that muramyl dipeptide-Lys (MDP-Lys), a lipophilic derivative of MDP,when either administered alone or encapsulatedin liposome membrane, has an inhibitory effect on lung metastasis of osteosarcoma in hamsters. The optimal dosage of MDP-Lys was found to be more than 50 mug/day when administeresteredalone and more than 20 mug, twice/weekwhen administeredas a liposome.
The following experimentwas conducted for the purpose of inhibiting primary tumore with the use of thermosensitive liposome encapsulated doxorubicin (ADR).
(1) Liposome was prepared with the use of dipalmitoylphosphatidyl choline : distearoylphosphatidyl choline in molar ratio 9 : 1 (DPPS : DSPC = 9 : 1). ADR was encapsulated by reverse-phase evaporation method and thermosensitive liposome encapsulated ADR was prepared.
(2) Transplantable osteosarcoma was transplanted in the calf muscle of the leg of 3-weeks old hamsters and the size of the tumor was measured 1,2, and 3 weeks after
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transplantation. This was employed as control group.
(3) The following four treatment methods were conducted one week after transplantation and by comparison with the control group antitumor effect was evaluated. Intravenous (i-v) administration of ADR was made in group A,localized hyper thermia of tumor in group B,i-v administration of ADR and localized hyperthermia of tumor in group C,and i-v administration of thermosensitive liposome encapsulated ADR and localized hyper-thermia of tumor in group D.The administereddosage of ADR was 5 mug/g. Hyperthermia was made for 30 minutes in warm bath of 43ﾟC and intratumor temperature was confifred by thermosensor inserted in the tumor.
2. (1) ADR encapsulation rate of thermosensitive liposome encapsulated ADR was approximately 20% and approximately 85% of entrapped ADR was released above 41ﾟC.
(2) The relative tumor growth rate two weeks after tumor transplantation (tumor volume two weeks after transplantation/tumorvolume one week after transplantation) was 13.5 (]SY.+-。[) 6.7 in the control group.
(3) The relative tumor growth rate two weeks after tumor transplantation (one week after treatment) was 6.8 (]SY.+-。[) 5.8 in group A,7.4 (]SY.+-。[) 4.3 in group B,6.7 (]SY.+-。[) 5.6 in group C,and 1.8 (]SY.+-。[) 0.5 in group D.Though tumor growth inhibition tendency was observed in group A,B,and C,but no significant difference could be demonstrated when compared to the control group. However, a significant antitumor effect was observedin group D (P<0.05). Less
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