Suzuki Sachiko, Kawakami Shigeru, Chansri Narin, Yamashita Fumiyoshi, Hashida Mitsuru
Department of Drug Delivery Research, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.
J Control Release. 2006 Nov;116(1):58-63. doi: 10.1016/j.jconrel.2006.08.025. Epub 2006 Sep 8.
The purpose of this study was to investigate whether all-trans retinoic acid (ATRA), an active metabolite of retinal, incorporated in cationic liposomes composed of 1,2 dioleoyl-3-trimethylammonium propane (DOTAP)/cholesterol could inhibit established metastatic lung tumors by delivery to the pulmonary tumor site after intravenous injection. After intravenous injection in mice, the highest lung accumulation of [(3)H]ATRA was observed by the DOTAP/cholesterol liposomes formulation, while other formulations including [(3)H]ATRA dissolved in serum or [(3)H]ATRA incorporated in distearoyl-l-phosphatidylcholine (DSPC)/cholesterol liposomes produced little accumulation in the lung. In mice used as a model of lung cancer metastasis, ATRA incorporated in DOTAP/cholesterol liposomes, injected intravenously, reduced the number of tumor nodules compared with free ATRA or ATRA incorporated in DSPC/cholesterol liposomes. These results suggest that ATRA incorporated in cationic liposomes would be an effective strategy for differentiation therapy of lung cancer metastasis.
本研究的目的是调查视黄醛的活性代谢产物全反式维甲酸（ATRA），掺入由1,2 - 二油酰基-3 - 三甲基氯化铵丙烷（DOTAP）/胆固醇组成的阳离子脂质体中，静脉注射后通过递送至肺肿瘤部位是否能够抑制已形成的转移性肺肿瘤。在小鼠静脉注射后，通过DOTAP/胆固醇脂质体制剂观察到[（3）H]ATRA在肺中的积累最高，而其他制剂，包括溶解于血清中的[（3）H]ATRA或掺入二硬脂酰磷脂酰胆碱（DSPC）/胆固醇脂质体中的[（3）H]ATRA在肺中几乎没有积累。在用作肺癌转移模型的小鼠中，静脉注射掺入DOTAP/胆固醇脂质体中的ATRA，与游离ATRA或掺入DSPC/胆固醇脂质体中的ATRA相比，减少了肿瘤结节的数量。这些结果表明，掺入阳离子脂质体中的ATRA将是肺癌转移分化治疗的有效策略。
