Liposomalization of SN-38 as active metabolite of CPT-11
Liposomalization of SN-38 as active metabolite of CPT-11
复制标题
DOI：
10.1016/j.jconrel.2005.08.023
复制
发表时间：
2005-11-28
影响因子：
10.8
通讯作者：
Sonobe, T
中科院分区：
文献类型：
--
作者：
Sadzuka, Y;Takabe, H;Sonobe, T
虽然已经开发了许多药物用于治疗疾病，但有些药物存在副作用等并发症，抗肿瘤药物应该更有选择性地靶向肿瘤或细胞。因此，有必要开发药物递送系统，并且据报道脂质体可用作有效的药物载体。抗肿瘤剂CPT-11通过抑制拓扑异构酶1抑制DNA合成，具有很强的抗肿瘤活性。SN-38由CPT-11转化为肝脏中的羧酸酯酶活性代谢产物。由于SN-38不溶，因此尚未在临床阶段作为注射剂应用。我们的目的是通过一种新的脂质体化方法使SN-38在临床上得到应用，从而扩大其他难溶性药物的应用范围。由于SN-38是疏水性的，因此尝试使用Bangham方法制备SN-38捕获的脂质体，该方法对一般制备有效。然而，没有实现脂质体中捕获的SN-38的高比率，并且这没有通过冻融方法或冷冻干燥方法得到改善。另一方面，通过改进的远程装载法，SN-38被捕获在脂质体中的比率约为Bangham法的4倍，并且通过膜装载法，脂质体制备的新方法，该比率分别达到改进的远程装载法和Bangham法的2倍和8倍，显示出显著增加。表明采用薄膜负载法制备的SN-38脂质体对SN-38有较好的包封效果。因此，预期SN-38脂质体可作为注射剂应用。如果可能应用于其他难溶性药物，则该制备方法是有用的。(c)2005 Elsevier B.V.保留所有权利。
Although many drugs have been developed for the treatment of disease, some drugs have complications such as adverse effects, and antitumor agents should target tumors or cells more selectively. It is therefore necessary to develop drug delivery systems, and liposomes are reportedly useful as an effective drug carrier. An antitumor agent, CPT-11, inhibits DNA synthesis by the inhibition of topoisomerasel and has a strong antitumor activity. SN-38 is converted from CPT-11 as an active metabolite by carboxylesterase in the liver. As SN-38 is insoluble, it has not been applied at the clinical stage as an injection. It is expected that SN-38 liposomalization may increase its usefulness in cancer chemotherapy.Our purpose is to have a clinical application of SN-38 by a novel method of liposomalization to expand the application for the other insolubility drugs. As SN-38 is hydrophobic, SN-38-trapped liposome preparation was attempted using the Bangham method, which is effective for general preparation. However, a high ratio of SN-38 trapped in liposome was not achieved, and this was not improved by the freezing-thawing method or the freeze-drying method. On the other hand, the ratio of SN-38 trapped in liposome by the modified remote loading method was about 4 times that by the Bangham method, and the ratio by the film loading method, novel method of liposomal preparation, reached 2 times and 8 times that by the modified remote loading method and Bangham method, respectively, showing a remarkable increase.In conclusion, it was suggested that the preparation of SN-38 liposome using the film loading method effectively entraps SN-38. Thus, it is expected that SN-38 liposome can be applied as an injection. This preparation method is useful if application is possible in the other insolubility drugs. (c) 2005 Elsevier B.V. All rights reserved.