Targetting therapy with liposome encapsulatedanticancerdrugin osteosarcoma on hamsters

1.本实验室以前的实验证明，胞壁酰二肽-赖氨酸（MDP-Lys）是MDP的亲脂性衍生物，单独给药或包封在脂质体膜中对骨肉瘤的肺转移有抑制作用。MDP-Lys单独给药的最佳剂量为50 μ g/天以上，脂质体给药的最佳剂量为20 μ g/周以上，2次/周。(1)使用摩尔比为9：1的二棕榈酰磷脂酰胆碱：二硬脂酰磷脂酰胆碱（DPPS：DSPC = 9：1）制备脂质体。采用逆相蒸发法对阿霉素进行包封，制备了阿霉素温敏脂质体。(2)将可移植性骨肉瘤移植于3周龄仓鼠小腿肌肉内，并于术后1、2、3周测量肿瘤大小 ...更多信息 移植以此作为对照组。(3)移植后一周进行以下四种治疗方法，并与对照组进行比较，评价抗肿瘤效果。A组静注ADR，B组静注ADR+肿瘤局部热疗，C组静注ADR+肿瘤局部热疗，D组静注ADR温敏脂质体+肿瘤局部热疗，ADR剂量为5 μ g/g。在43 ℃的温浴中加热30分钟，通过插入肿瘤内的温度传感器确定瘤内温度. (1)温敏脂质体包封ADR的包封率约为20%，在41 ℃以上释放约85%。(2)肿瘤移植后2周的相对肿瘤生长率（移植后2周的肿瘤体积/移植后1周的肿瘤体积）为13.5（± SD）。对照组6.7。(3)肿瘤移植后两周（治疗后一周）的相对肿瘤生长率为6.8（±）SY。A组5.8 ± 0.05，B组7.4 ± 0.05。B组4.3例，6.7例（± SD）。C组为5.6 ± 1.8（± 0.001），P < 0.01。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性差异。D组抑瘤作用显著（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