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Pharm Res. 2012 Jul;29(7):1882-96. doi: 10.1007/s11095-012-0714-8. Epub 2012 Mar 27.
Novel surfactants made of diglutamic acid (DG) polar head linked to lithocholic, arachidonic, linoleic or stearic acids were designed for drug solubilization.
Surfactants 3-D conformer and packing parameter were determined by molecular modelling and self-assembling properties by pyrene fluorescence measurements. Cytotoxicity was assessed on Human Umbilical Vein Endothelial Cells (HUVEC) and haemolyitic activity on rat red blood cells. Drug solubilization was quantified and its interaction with hydrophobic moieties was characterized using differential scanning calorimetry and X-ray diffraction. Self organisation of stearoyl-DG was observed by cryogenic transmission electron microscopy. Toxicity after repeated injections of stearoyl-DG was investigated in Wistar rats.
DG-based surfactants self-assemble into water and their critical micellar concentrations are comprised between 200 and 920 μg/mL. Cytotoxicity and haemolysis were lower than for polysorbate 80. At best, stearoyl-DG solubilized the drug up to 22% (w/w). Solid-state characterization evidenced drug/lipid interactions leading to the formation of a new complex. Stearoyl-DG formed spherical micelles of 20 nm, as predicted by packing parameter calculation. However, it induced a possible liver toxicity after intravenous administration in rats.
Among the surfactants tested, stearoyl-DG is the more efficient for drug solubilization but its use is limited by its possible liver toxicity.
设计了由二谷氨酸（DG）极性头与石胆酸、花生四烯酸、亚油酸或硬脂酸连接而成的新型表面活性剂，用于药物增溶。
通过分子建模确定了表面活性剂的 3-D 构象和堆积参数，并通过芘荧光测量确定了自组装特性。在人脐静脉内皮细胞（HUVEC）上评估细胞毒性，在大鼠红细胞上评估溶血活性。通过差示扫描量热法和 X 射线衍射量化药物增溶，并对其与疏水性基团的相互作用进行了表征。通过低温透射电子显微镜观察了硬脂酰-DG 的自组织。在 Wistar 大鼠中研究了重复注射硬脂酰-DG 后的毒性。
基于 DG 的表面活性剂在水中自组装，其临界胶束浓度在 200 至 920μg/mL 之间。细胞毒性和溶血活性低于聚山梨酯 80。硬脂酰-DG 对药物的增溶效果最佳，可达 22%（w/w）。固态特征表明药物/脂质相互作用导致形成新的复合物。根据堆积参数计算，硬脂酰-DG 形成了 20nm 的球形胶束。然而，它在大鼠静脉内给药后可能引起肝脏毒性。
在所测试的表面活性剂中，硬脂酰-DG 是药物增溶效率最高的，但由于其可能的肝脏毒性，其使用受到限制。
