Preparation and biological properties of dichloro(1,2-diaminocyclohexane)platinum(II) (DACHPt)-loaded polymeric micelles
Preparation and biological properties of dichloro(1,2-diaminocyclohexane)platinum(II) (DACHPt)-loaded polymeric micelles
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DOI：
10.1016/j.jconrel.2004.08.022
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发表时间：
2005-01-03
影响因子：
10.8
通讯作者：
Kataoka, K
中科院分区：
文献类型：
--
作者：
Cabral, H;Nishiyama, N;Kataoka, K
通过 DACHPt 与聚（乙二醇）-聚（谷氨酸）嵌段共聚物 [PEG-P(Glu)] 在蒸馏水中形成聚合物-金属络合物，制备了含有二氯（1,2-二氨基环己烷）铂（II）（DACHPt）（奥沙利铂母体复合物）的嵌段共聚物胶束。通过动态光散射(DLS)测量，确定胶束尺寸为40nm，分布较窄。在 37 摄氏度的磷酸盐缓冲盐水 (pH 7.4) 中测量铂复合物从胶束核心的释放。负载 DACHPt 的胶束在 12 小时的诱导期后显示出铂的持续释放速率。在相同条件下，测量了负载 DACHPt 的胶束的动力学稳定性。发现胶束非常稳定，在 240 小时内保持初始尺寸。针对鼠结肠腺癌 26 (C-26) 细胞，负载 DACHPt 的胶束表现出相当大的体外细胞毒性，低于奥沙利铂，但由于胶束中铂络合物的释放，随着暴露时间的延长而增加。对荷瘤小鼠进行的体内生物分布测定表明，胶束由于其高稳定性和长时间的高肿瘤积累而表现出延长的血液循环。 (c) 2004 Elsevier B.V. 保留所有权利。
Block copolymer micelles, containing dichloro(1,2-diaminocyclohexane)platinum(II) (DACHPt), the oxaliplatin parent complex, were prepared through polymer-metal complex formation of DACHPt with poly(ethylene glycol)-poly(glutamic acid) block copolymer [PEG-P(Glu)] in distilled water. By dynamic light scattering (DLS) measurement, the micelle size was determined to be 40 run with narrow distribution. The release of platinum complexes from the micelle core was measured in phosphate buffer saline (pH 7.4) at 37 degrees C. DACHPt-loaded micelle showed a sustained release rate of platinum after an induction period of 12 h. In the same conditions, the kinetic stability of DACHPt-loaded micelle, was measured. The micelle was found to be very stable, keeping the initial size, for 240 h. Against murine colon adenocarcinoma 26 (C-26) cells, DACHPt-loaded micelle exhibited considerable in vitro cytotoxicity, lower than oxaliplatin but increasing with exposure time as a result of the release of platinum complexes from the micelle. In vivo biodistribution assay performed on tumor-bearing mice demonstrated that the micelle showed prolonged blood circulation due to its high stability and high tumor accumulation for a prolonged time. (c) 2004 Elsevier B.V. All rights reserved.