Department of Applied Chemistry, Graduate School of Engineering, Kyushu University, 744 Moto-oka, Fukuoka 819-0395, Japan.
J Colloid Interface Sci. 2010 Dec 1;352(1):136-42. doi: 10.1016/j.jcis.2010.08.035. Epub 2010 Aug 13.
In this paper, we report a novel ionic liquid-in-oil (IL/o) microemulsion which is able to dissolve pharmaceuticals that are insoluble or sparingly soluble in water and most of pharmaceutical grade organic liquids. Towards this approach, the nanometer-sized ionic liquid droplets in isopropyl myristate (IPM) were formed with a blend of nonionic surfactants, polyoxyethylene sorbitan monooleate (Tween-80), and sorbitan laurate (Span-20). A set of ionic liquids (ILs) was tested as a dispersed phase, and it was observed that ILs possessing coordinating anions which are strong hydrogen bond acceptor were most effective in forming microemulsion droplets. The possible formation mechanism was also studied. Ternary phase behavior study clearly indicated the formation of optically transparent and thermodynamically stable microemulsions with a wide range of IL content. The shape, size and size distribution of the aggregates in microemulsions were characterized using dynamic light scattering (DLS), which demonstrated the formation of spherical micelles in the range of 8-34nm. In order to explore the use of newly developed microemulsion as a potential drug carrier, we have investigated the solubility of some drug molecules (e.g., acyclovir, methotrexate and 1-[(5-(p-nitrophenyl) furfurylidene) amino] hydantoin sodium) that are insoluble or sparingly soluble in most of the conventional solvents. Very significantly, the solubility studies indicated a high degree of solubilization of such drugs in IL microemulsions. We believe that this microemulsion formed with ILs having the unique physical, chemical and biological properties may offer novel opportunities to develop a potential drug delivery carrier for poorly soluble drugs molecules.
本文报道了一种新型的离子液体-油（IL/o）微乳液，它能够溶解在水中以及大多数药物级有机溶剂中不溶或难溶的药物。为此，采用非离子表面活性剂聚氧乙烯失水山梨醇单油酸酯（Tween-80）和失水山梨醇月桂酸酯（Span-20）的混合物，在肉豆蔻酸异丙酯（IPM）中形成纳米级的离子液体液滴。测试了一系列离子液体（ILs）作为分散相，结果表明，具有强氢键受体配位阴离子的 ILs 最有效地形成微乳液液滴。还研究了可能的形成机制。三元相态行为研究清楚地表明，在具有宽 IL 含量范围的情况下形成了光学透明和热力学稳定的微乳液。使用动态光散射（DLS）对微乳液中聚集体的形状、大小和分布进行了表征，结果表明在 8-34nm 的范围内形成了球形胶束。为了探索新开发的微乳液作为潜在药物载体的用途，我们研究了一些药物分子（如阿昔洛韦、甲氨蝶呤和 1-[(5-(对硝基苯基)糠基)亚氨基]海因钠）的溶解度，这些药物在大多数常规溶剂中不溶或难溶。非常显著的是，溶解度研究表明，这些药物在 IL 微乳液中有很高的溶解度。我们相信，这种具有独特物理、化学和生物特性的离子液体形成的微乳液可能为开发难溶性药物分子的潜在药物输送载体提供新的机会。
