Novel and simple loading procedure of cisplatin into liposomes and targeting tumor endothelial cells
Novel and simple loading procedure of cisplatin into liposomes and targeting tumor endothelial cells
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DOI：
10.1016/j.ijpharm.2010.02.030
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发表时间：
2010-05-31
影响因子：
5.8
通讯作者：
Seno, M.
中科院分区：
文献类型：
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作者：
Hirai, M.;Minematsu, H.;Seno, M.
虽然静脉注射高浓度顺铂（CDDP）由于其严重的副作用而受到限制，但将CDDP直接有效地递送到肿瘤应该改善治疗反应，同时潜在地绕过显著的副作用。由于顺式二氨二硝酸铂（CDDP 3）在水中高度可溶，并且在氯离子存在下转化为CDDP，我们在不存在氯离子的情况下将CDDP 3包封到脂质体中，并补充氯离子以制备CDDP包封脂质体（CDDP-Lip），从而显著提高COOP的负载效率。我们进一步将CDDP-Lip与Sialyl刘易斯（X）缀合（CDDP-SLX-Lip），因为我们先前证明了Sialyl刘易斯（X）增强脂质体在体内肿瘤中的有效积累。即使将致死水平的CDDP注射到小鼠中，CDDP-SLX-Lip处理的小鼠在14天显示75%的存活率。体重减轻可忽略不计，在各种正常组织中未发现组织学异常。CDDP-SLX-Lip的蓄积量是CDDP-Lip或CDDP的约6倍。结果表明，CDDP-SLX-Lip的抗肿瘤活性明显优于CDDP-Lip，且对正常组织的毒性作用明显低于CDDP-Lip。(C)2010 Elsevier B. V.保留所有权利。
Although intravenous administration of high levels of cisplatin (CDDP) are limited due to its severe side effects, efficient delivery of CDDP directly to the tumor should improve the therapeutic response while potentially by-passing significant side effects.High loading of CDDP into liposomes is one technique that could be used as a potential drug delivery system. Since cis-diamminedinitratoplatinum (CDDP3) is highly soluble in water and converts to CDDP in the presence of chloride ions, we encapsulated CDDP3 into liposomes in the absence of chloride ions and supplemented chloride ions to prepare CDDP-encapsulated liposomes (CDDP-Lip) resulting in a significantly improved loading efficiency of COOP. We further conjugated the CDDP-Lip with Sialyl Lewis(X) (CDDP-SLX-Lip) because we previously demonstrated Sialyl Lewis(X) enhanced efficient accumulation of liposomes into tumors in vivo. CDDP-SLX-Lip treated mice showed a survival rate of 75% at 14 days even if a lethal level of CDDP was injected into mice. Loss of body weight was negligible and no histological abnormality was found in a variety of normal tissues. Accumulation of CDDP-SLX-Lip was about 6 times more than that of CDDP-Lip or CDDP. As the result, there was better antitumor activity of CDDP-SLX-Lip than that of CDDP-Lip with significantly less toxic effects in normal tissues. (C) 2010 Elsevier B.V. All rights reserved.