Forssen E A, Coulter D M, Proffitt R T
Vestar, Inc., San Dimas, California 91773.
Cancer Res. 1992 Jun 15;52(12):3255-61.
Small unilamellar vesicles (SUVs), consisting of highly purified distearoyl phosphatidylcholine and cholesterol (2:1 mol ratio) selectively increased the delivery of entrapped daunorubicin to solid tumors in vivo. When measured against free drug, SUV-entrapped daunorubicin produced a nearly 10-fold increase in tumor uptake and efficacy when used to treat a murine lymphosarcoma model (P-1798). In a second murine solid tumor model, MA16C mammary adenocarcinoma, the median survival time for daunorubicin SUV treatment at 2 mg/kg (72 days) was equivalent to the median survival time for the free drug optimal dose, 20 mg/kg (70 days), again indicating a 10-fold increased therapeutic efficacy. When compared at maximum efficacious doses in the MA16C model, the proportion of long-term survivors was greater with daunorubicin SUVs: 10 long-term survivors of 10 mice treated with daunorubicin SUVs at 25 mg/kg versus 4 long-term survivors of 10 mice treated with free drug at 20 mg/kg. The lowest toxic doses for MA16C tumor-bearing animals (treatment median survival times less than controls) were 25 mg/kg for free drug and 40 mg/kg for daunorubicin SUVs. The demonstration of enhanced antineoplastic activity and an increased tolerance for daunorubicin suggests that this specific SUV composition may be an effective delivery system for a wide range of chemotherapeutic agents in the treatment of solid tumors.
由高度纯化的二硬脂酰磷脂酰胆碱和胆固醇（摩尔比2:1）组成的小单层囊泡（SUVs）在体内选择性地增加了包裹的柔红霉素向实体瘤的递送。与游离药物相比，当用于治疗小鼠淋巴肉瘤模型（P-1798）时，包裹在SUVs中的柔红霉素在肿瘤摄取和疗效方面提高了近10倍。在第二个小鼠实体瘤模型MA16C乳腺腺癌中，柔红霉素SUV以2mg/kg剂量治疗的中位生存时间（72天）与游离药物最佳剂量20mg/kg的中位生存时间（70天）相当，再次表明治疗效果提高了10倍。在MA16C模型中以最大有效剂量进行比较时，柔红霉素SUVs的长期存活者比例更高：25mg/kg的柔红霉素SUVs治疗的10只小鼠中有10只长期存活，而20mg/kg的游离药物治疗的10只小鼠中有4只长期存活。携带MA16C肿瘤的动物的最低毒性剂量（治疗中位生存时间短于对照组），游离药物为25mg/kg，柔红霉素SUVs为40mg/kg。柔红霉素抗肿瘤活性增强和耐受性增加的证明表明，这种特定的SUV组成可能是一种有效的递送系统，用于治疗实体瘤的多种化疗药物。
