High-loading nanosized micelles of copoly(styrene-maleic acid)-zinc protoporphyrin for targeted delivery of a potent heme oxygenase inhibitor
High-loading nanosized micelles of copoly(styrene-maleic acid)-zinc protoporphyrin for targeted delivery of a potent heme oxygenase inhibitor
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DOI：
10.1016/j.biomaterials.2006.11.051
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发表时间：
2007-04-01
期刊：
影响因子：
14
通讯作者：
Maeda, Hiroshi
中科院分区：
文献类型：
--
作者：
Iyer, Arun K.;Greish, Khaled;Maeda, Hiroshi
两亲性苯乙烯-马来酸（SMA）共聚物与血红素加氧酶催化剂锌原卟啉（ZnPP）形成胶束。胶束的构建通过微妙的pH值的调节，形成疏水性ZnPP和两亲性SMA之间的非共价相互作用。由此形成的胶束（SMA-ZnPP）是在水中具有窄尺寸分布（平均直径176.5nm）的纳米颗粒，具有可调负载（从15%w/w到60%w/w的ZnPP）和显著的水溶性。通过尺寸排阻色谱（SEC）测定，SMA-ZnPP的平均分子量为144 kDa，该尺寸比游离ZnPP的分子量（626.03Da）显著增加，表明形成了胶束结构。胶束显示出恒定的ZnPP释放率约0.5%/天，在体外中性pH值。SMA-ZnPP胶束抑制脾微粒体HO-1活性，在竞争性和剂量依赖性的方式，与0.12 μ m的表观抑制常数（Ki），相当于游离ZnPP，也表现出显着的细胞毒性作用KYSE-510人食管癌细胞。SMA-ZnPP胶束的独特特征在于它们是水溶液中的纳米颗粒，具有高水溶性和负载，但本质上是大分子，这可以有益于有效HO-1抑制剂的靶向释放。(c)2006爱思唯尔有限公司版权所有。
Amphiphilic styrene-maleic acid (SMA) copolymer efficiently formed micelles with a potent heme oxygenase inhibitor-zinc protoporphyrin (ZnPP). The micelles were constructed by subtle pH adjustments to form non-covalent interaction between the hydrophobic ZnPP and amphiphilic SMA. The micelles (SMA-ZnPP) thus formed were nanoparticles with narrow size distribution in water (mean diameter 176.5nm), having tunable loading (from 15% to 60% w/w of ZnPP) with remarkable aqueous solubility. SMA-ZnPP had an average molecular size of 144kDa as determined by size-exclusion chromatography (SEC), this size is a marked increase from the molecular weight of free ZnPP (626.03Da), suggesting the formation of micellar structure. The micelles showed a constant ZnPP release rate of about 0.5%/day in vitro at neutral pH. SMA-ZnPP micelles inhibited splenic microsomal HO-1 activity, in a competitive and dose-dependent manner, with an apparent inhibitory constant (K-i) of 0.12 mu m, comparable to free ZnPP and also exhibited marked cytotoxic effect on KYSE-510 human esophageal cancer cells. The unique features of SMA-ZnPP micelles are that they are nanoparticles in aqueous solution having high water solubility and loading, yet macromolecular in nature, which can be beneficial in targeted release of a potent HO-1 inhibitor. (c) 2006 Elsevier Ltd. All rights reserved.