Shimizu Kazuyuki, Tamagawa Kayoko, Takahashi Noriko, Takayama Kozo, Maitani Yoshie
Department of Pharmaceutics, Hoshi University, Ebara 2-4-41, Shinagawa-ku, 142, Tokyo, Japan.
Int J Pharm. 2003 Jun 4;258(1-2):45-53. doi: 10.1016/s0378-5173(03)00151-0.
The aim of this study was to develop an intravenous delivery of all-trans retinoic acid (ATRA) for the treatment of cancer. Two kinds of liposomes composed of dipalmitoylphosphatidylcholine and cholesterol with sterylglucoside (SG) mixture (SG liposomes) or without SG (non-SG liposomes) were prepared. A limited amount of ATRA was incorporated into liposomes approximately 3mol%. ATRA-loaded SG liposomes were more stable at 4 degrees C with light protection for 24 days than non-SG liposomes; maintaining 83.1% ATRA and the average diameter 198.5 nm (36 days), and in 80% rat serum for 120 min. SG seems to increase the ATRA-loaded efficiency in liposomes and stability of liposomes compared with cholesterol. The mean survival time of mice given SG liposomes (18.2 days) indicated a greater antitumor activity than saline (14.1 days) (P<0.001) without change of mean body weight. It is concluded that the current ATRA-loaded SG liposomes are potentially applicable for hepatic metastasis of M5076 tumor.
本研究的目的是开发一种用于治疗癌症的全反式维甲酸（ATRA）静脉给药方式。制备了两种由二棕榈酰磷脂酰胆碱和胆固醇与甾醇糖苷（SG）混合物组成的脂质体（SG脂质体）或不含SG的脂质体（非SG脂质体）。将有限量的ATRA以约3mol%的比例掺入脂质体中。负载ATRA的SG脂质体在4℃下在有光保护的情况下比非SG脂质体更稳定24天；在36天内保持83.1%的ATRA且平均直径为198.5nm，并在80%大鼠血清中保持120分钟。与胆固醇相比，SG似乎提高了脂质体中ATRA的负载效率和脂质体的稳定性。给予SG脂质体的小鼠平均生存时间（18.2天）显示出比盐水（14.1天）更大的抗肿瘤活性（P<0.001），且平均体重无变化。结论是，目前负载ATRA的SG脂质体可能适用于M5076肿瘤的肝转移。
