Core-cross-linked polymeric micelles as paclitaxel carriers
Core-cross-linked polymeric micelles as paclitaxel carriers
复制标题
DOI：
10.1021/bc034113u
复制
发表时间：
2004-05-01
影响因子：
4.7
通讯作者：
Kissel, T
中科院分区：
文献类型：
--
作者：
Shuai, XT;Merdan, T;Kissel, T
合成了聚己内酯（PCL）与单甲氧基聚乙二醇（MPEG）的交联二嵌段和三嵌段共聚物。这些两亲性共聚物在水溶液中自组装成能够将疏水紫杉醇包封在其疏水核中的纳米胶束。为了进一步提高其热力学稳定性，胶束通过引入PCL嵌段的双键的自由基聚合进行交联。发现反应条件显著影响交联效率和胶束尺寸。质子核磁共振（H-1 NMR）谱证实了紫杉醇进入胶束的包裹。令人鼓舞的是，胶束的紫杉醇负载效率显着提高胶束核交联。胶束的大小和载药效率都随着PCL嵌段长度的增加而显著增加，无论胶束是否为核交联的。然而，紫杉醇负载并没有明显影响胶束的大小或大小分布。交联胶束表现出显着增强的热力学稳定性，对稀释与水性溶剂。通过共聚焦激光扫描显微镜（CLSM）成像证实了载于纳米胶束中的紫杉醇的有效细胞摄取。这种新的可生物降解的纳米级载体系统值得进一步研究胃肠外给药。
Cross-linkable di- and triblock copolymers of poly(c-caprolactone) (PCL) and monomethoxyl poly(ethylene glycol) (MPEG) were synthesized. These amphiphilic copolymers self-assembled into nanoscale micelles capable of encapsulating hydrophobic paclitaxel in their hydrophobic cores in aqueous solutions. To further enhance their thermodynamic stability, the micelles were cross-linked by radical polymerization of the double bonds introduced into the PCL blocks. Reaction conditions were found to significantly affect both the cross-linking efficiency and the micelle size. The encapsulation of paclitaxel into the micelles was confirmed by the proton nuclear magnetic resonance (H-1 NMR) spectroscopy. Encouragingly, paclitaxel-loading efficiency of micelles was enhanced significantly upon micelle core-cross-linking. Both the micelle size and the drug loading efficiency increased markedly with increasing the PCL block lengths, no matter if the micelles were core-crosslinked or not. However, paclitaxel-loading did not obviously affect the micelle size or size distribution. The cross-linked micelles exhibited a significantly enhanced thermodynamic stability against dilution with aqueous solvents. The efficient cellular uptake of paclitaxel loaded in the nanomicelles was demonstrated by confocal laser scanning microscopy (CLSM) imaging. This new biodegradable nanoscale carrier system merits further investigations for parenteral drug delivery.