Targetting therapy with liposome encapsulatedanticancerdrugin osteosarcoma on hamsters

1. 我们之前的实验已经证明，MDP的亲脂衍生物muramyl二肽- lys （MDP- lys）单独给药或包封在脂质体膜中对仓鼠骨肉瘤肺转移有抑制作用。当单独给药时，最佳剂量大于50马克杯/天；当作为脂质体给药时，最佳剂量大于20马克杯/周2次。本实验采用热敏脂质体包封阿霉素（ADR）抑制原发肿瘤。(1)以双棕榈酰磷脂酰胆碱与二硬脂酰磷脂酰胆碱的摩尔比为9:1 （DPPS: DSPC = 9:1）制备脂质体。采用反相蒸发法包封ADR，制备了热敏脂质体包封ADR。(2)将可移植骨肉瘤移植于3周龄的仓鼠小腿肌肉，并在1、2、3周后测量肿瘤的大小。作为对照组。(3)移植后1周采用以下4种治疗方法，与对照组比较，评价其抗肿瘤效果。A组静脉滴注ADR， B组局部热疗肿瘤，C组静脉滴注ADR并局部热疗肿瘤，d组静脉滴注热敏脂质体包裹ADR并局部热疗肿瘤。ADR给药剂量为5杯/g。2.在43℃温浴中热疗30分钟，通过植入肿瘤的热传感器确认肿瘤内温度。(1)热敏脂质体包裹ADR的ADR包封率约为20%，约85%的ADR包封在41℃以上释放。(2)肿瘤移植后2周肿瘤相对生长率（移植后2周肿瘤体积/移植后1周肿瘤体积）为13.5 (]SY.+-。[)对照组6.7。(3)肿瘤移植后2周（治疗后1周）肿瘤相对生长率为6.8 （]SY.+-）。[] A组5.8分，7.4分。[) B组4.3,[]SY.+-。[] C组为5.6,[]SY.+-。[) d组0.5，A、B、C组虽有抑制肿瘤生长的趋势，但与对照组比较无显著差异。D组抗肿瘤效果显著（P<0.05）。少

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