Influence of serum protein on polycarbonate-based copolymer micelles as a delivery system for a hydrophobic anti-cancer agent
Influence of serum protein on polycarbonate-based copolymer micelles as a delivery system for a hydrophobic anti-cancer agent
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DOI：
10.1016/j.jconrel.2004.12.013
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发表时间：
2005-03-21
影响因子：
10.8
通讯作者：
Allen, C
中科院分区：
文献类型：
--
作者：
Liu, JB;Zeng, FQ;Allen, C
研究了由甲氧基（聚乙二醇）-b-聚（5-苄氧基-三亚甲基碳酸酯; MePEG-B-PBTMC 5000-B-4800）形成的新胶束系统作为疏水性抗癌剂椭圆藤碱的递送系统。使用高压挤出技术将椭圆藤碱负载到MePEG-b-PBMC胶束中，负载效率为95%。椭圆藤碱负载胶束具有球形形态和96 nm的平均直径。证实在MePEG-b-PBMC胶束中配制后保留了椭圆藤碱的抗癌活性。通过透射电子显微镜、动态光散射和凝胶过滤色谱研究了MePEG-b-PBMC胶束对蛋白质的吸附程度。总的来说，发现与胶束松散和紧密结合的蛋白质的量是最小且不显著的。在一系列蛋白质浓度范围内检查椭圆藤碱在含有蛋白质的水性介质和MePEG-b-PBMC胶束之间的分配特性。在生理相关条件下，发现61%的药物保留在胶束部分内，而39%在含蛋白质的水相中。此外，椭圆藤碱从胶束的体外药物释放曲线拟合使用修改的Higuchi模型，并发现在蛋白质的存在下，加速。这些研究表明，尽管胶束和蛋白质之间没有显著的相互作用，但胶束作为递送载体的性质可能受到蛋白质-药物相互作用的强烈影响。(c)2004 Elsevier B. V.保留所有权利。
A new micelle system formed from methoxy (polyethylene glycol)-b-poly (5-benzyloxy-trimethylene carbonate; MePEG-b-PBTMC 5000-b-4800) was investigated as a delivery system for the hydrophobic anti-cancer agent, ellipticine. The ellipticine was loaded into the MePEG-b-PBTMC micelles with a loading efficiency of 95% using a high-pressure extrusion technique. The ellipticine-loaded micelles have a spherical morphology and an average diameter of 96 nm. The anti-cancer activity of ellipticine was confirmed to be retained following formulation in the MePEG-b-PBTMC micelles. The extent of protein adsorption to the MePEG-b-PBTMC micelles was investigated by transmission electron microscopy, dynamic light scattering and gel filtration chromatography. Overall, the amount of protein both loosely and tightly associated with the micelles was found to be minimal and insignificant. The partitioning properties of ellipticine between an aqueous medium containing protein and the MePEG-b-PBTMC micelles were examined over a range of protein concentrations. Under physiologically relevant conditions, it was found that 61% of the drug remained within the micelle fraction while 39% was in the protein-containing aqueous phase. In addition, the in vitro drug release profile of ellipticine from the micelles was fit using a modified Higuchi model and found to be accelerated in the presence of protein. These studies demonstrate that although there are no significant interactions between micelle and protein, the properties of the micelle as a delivery vehicle may be strongly influenced by protein-drug interactions. (c) 2004 Elsevier B.V. All rights reserved.