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Targetting therapy with liposome encapsulatedanticancerdrugin osteosarcoma on hamsters

脂质体封装抗癌药物对仓鼠骨肉瘤的靶向治疗

基本信息

批准号：
08671663
负责人：
SUGITA Takashi
金额：
$ 1.41万
依托单位：
HIROSHIM UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1996
资助国家：
日本
起止时间：
1996 至 1997
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08671663/
关键词：
Muramyl dipeptide Osteosarcoma Liposomes Hamsters Thermosensitive Doxorubicin Localized hyperthermia Controled release

项目摘要

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 … More 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

1. 我们前期的实验表明，胞壁酰二肽-Lys（MDP-Lys）是MDP的亲脂性衍生物，无论单独给药还是封装在脂质体膜中，对仓鼠骨肉瘤肺转移都有抑制作用。研究发现，单独给药时，MDP-Lys的最佳剂量为大于50微克/天，以脂质体给药时，为大于20微克/周两次。为了利用热敏脂质体封装的阿霉素(ADR)抑制原发性肿瘤，进行了以下实验。 (1)使用以下物质制备脂质体：二棕榈酰磷脂酰胆碱：二硬脂酰磷脂酰胆碱，摩尔比为 9:1 (DPPS:DSPC = 9:1)。采用反相蒸发法封装ADR，制备热敏脂质体封装ADR。(2)将可移植性骨肉瘤移植到3周龄仓鼠小腿小腿肌肉中，移植后1、2、3周测量肿瘤大小。将此作为对照组。(3)移植后1周进行以下四种治疗方法，并通过与对照组比较来评价抗肿瘤效果。 A组静脉注射ADR，B组静脉注射ADR+肿瘤局部热疗，C组静脉注射ADR+肿瘤局部热疗，D组静脉注射热敏脂质体包裹的ADR+肿瘤局部热疗。ADR给药剂量为5μg/g。 43℃温浴热疗30分钟，通过插入肿瘤的热传感器确认瘤内温度。2． (1)热敏脂质体封装的ADR的ADR包封率约为20%，包埋的ADR在41℃以上释放约85%。(2)肿瘤移植后两周的相对肿瘤生长率(移植后两周的肿瘤体积/移植后一周的肿瘤体积)为13.5(]SY.+-。[)对照组为6.7。(3)肿瘤移植后的相对肿瘤生长率肿瘤移植后两周（治疗后1周）生长率为A组6.8（]SY.+-。[）5.8，B组7.4（]SY.+-。[）4.3，C组6.7（]SY.+-。[）5.6，D组1.8（]SY.+-。[）0.5。虽然A、B、C组均观察到肿瘤生长抑制趋势，但无明显差异。差异可能是与对照组相比得到证实。但D组有显着的抗肿瘤作用（P<0.05）。较少的