In vitro characterization of PEGylated phospholipid micelles for improved drug solubilization:: Effects of PEG chain length and PC incorporation
In vitro characterization of PEGylated phospholipid micelles for improved drug solubilization:: Effects of PEG chain length and PC incorporation
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DOI：
10.1002/jps.20150
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发表时间：
2004-10-01
影响因子：
3.8
通讯作者：
Önyüksel, H
中科院分区：
文献类型：
--
作者：
Ashok, B;Arleth, L;Önyüksel, H
由聚乙二醇-2000接枝的二硬脂酰磷脂酰乙醇胺（DSPE-PEG）构成的空间稳定胶束（SSM）和由DSPE-PEG和卵磷脂（PC）构成的空间稳定混合胶束（SSMM）是近年来发展起来的新型水不溶性药物脂质载体。然而，影响这些磷脂增溶行为的因素很多。胶束还没有被很好地理解。研究了PEG链长和PC含量对PEG化磷脂胶束的物理性质和增溶潜力的影响。使用荧光探针测定的具有不同PEG链长（2000、3000和5000）的DSPE-PEG的临界胶束浓度（CMC）在微摩尔范围（0.5-1.5 μ M）内，对于较长的PEG链长具有较高的CMC。准弹性光散射（QELS）法测定胶束尺寸表明，当PC的加入量分别大于或等于25%（DSPE-PEG 2000）和大于或等于40%（DSPE-PEG 5000）时，胶束体系变得不均匀。以上这些临界PC比率的聚集数和棒状粒子的形成显着增加，观察到小角中子散射（SANS）。地西泮的溶解。用反相高效液相色谱法测定，DSPE-PEG 2000的胶束比DSPE-PEG 5000简单胶束更大。然而，DSPE-PEG 5000胶束表现出更大的改善，在水不溶性药物的增溶与PC含量的增加。总之，磷脂胶束的大小和增溶潜力与PEG链长和PC含量的混合胶束。胶束的聚集数和形状没有显着变化，直到临界PC浓度。(C)2004 Wiley-Liss，Inc.
Sterically stabilized micelles (SSM) composed of poly(ethylene glycol-2000)-grafted distearoylphosphatidylethanolamine (DSPE-PEG) and sterically stabilized mixed micelles (SSMM) composed of DSPE-PEG and egg-phosphatidyl choline (PC) have recently been introduced as novel lipid based carriers for water-insoluble drugs. However, factors that affect the solubilization behavior of these phospholipid. micelles are not well understood. This study investigates the effect of PEG chain length and PC content on physical properties and solubilization potential of PEGylated phospholipid micelles. Critical micelle concentrations (CMC) determined for DSPE-PEG with different PEG chain lengths (2000, 3000, and 5000) using a fluorescent probe were in the micromolar range (0.5-1.5 muM) with higher CMC for longer PEG chain length. The size of micelles determined by quasi-elastic light scattering (QELS) showed that micellar systems became heterogeneous when PC was added at greater than or equal to25% for DSPE-PEG 2000 and greater than or equal to40% for DSPE-PEG 5000, respectively. Above these critical PC ratios a significant increase in aggregation number and formation of rodlike particles were observed by small angle neutron scattering (SANS). Solubilization of diazepam. was greater with DSPE-PEG 2000 than DSPE-PEG 5000 simple micelles as determined by RP-HPLC. However, DSPE-PEG 5000 micelles showed greater improvement in solubilization of the water-insoluble drug with an increase in PC content. In conclusion, phospholipid micelle size and solubilization potential varied with PEG chain length and PC content in the mixed micelle. Aggregation number and shape of the micelles did not significantly change until the critical PC concentrations. (C) 2004 Wiley-Liss, Inc.