The third evolution of ionic liquids:: active pharmaceutical ingredients
The third evolution of ionic liquids:: active pharmaceutical ingredients
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DOI：
10.1039/b706677p
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发表时间：
2007-01-01
影响因子：
3.3
通讯作者：
Rogers, Robin D.
中科院分区：
文献类型：
--
作者：
Hough, Whitney L.;Smiglak, Marcin;Rogers, Robin D.
模块化，基于离子液体（IL）的策略允许划分分子水平设计广泛的新材料，具有可调的生物特性，以及众所周知的物理和化学特性，因此值得考虑作为具有新型性能增强和递送选项的“可调”活性药物成分（api）。IL策略可以利用IL的双重性质（离散离子）来实现增强，包括控制溶解度（例如，亲水性和疏水性IL都是可能的），生物利用度或生物活性，稳定性，消除多态性，新的递送选择（例如，缓慢释放或IL- API作为“溶剂”），甚至定制药物鸡尾酒。在这里，我们举例说明了这种方法，其中包括利多卡因（LD），一种疏水性室温IL，与盐酸利多卡因相比，在两种不同的小鼠抗痛觉模型中，它表现出改变的溶解度，增加的热稳定性和显著增强的局部镇痛效果。神经生长因子抑制神经元di的研究。大鼠嗜铬细胞瘤（PC12）细胞的猝灭提示LD和盐酸利多卡因在细胞水平上的潜在差异，表明其作用机制完全不同。综上所述，这些结果表明，一般来说，由于（至少）缓释特性以及新的递送机制，il独特的物理化学特性可能会赋予原料药新的生物活性。
A modular, ionic liquid ( IL)- based strategy allows compartmentalized molecular level design of a wide range of new materials with tunable biological, as well as the well known physical and chemical, properties of ILs, which thus deserve consideration as ` tunable' active pharmaceutical ingredients ( APIs) with novel performance enhancement and delivery options. IL strategies can take advantage of the dual nature ( discrete ions) of ILs to realize enhancements which may include controlled solubility ( e. g., both hydrophilic and hydrophobic ILs are possible), bioavailability or bioactivity, stability, elimination of polymorphism, new delivery options ( e. g., slow release or the IL- API as 'solvent'), or even customized pharmaceutical cocktails. Here we exemplify this approach with, among others, lidocaine docusate ( LD), a hydrophobic room temperature IL which, when compared to lidocaine hydrochloride, exhibits modfied solubility, increased thermal stability, and a significant enhancement in the e. cacy of topical analgesia in two different models of mouse antinociception. Studies of the suppression of nerve growth factor mediated neuronal di. erentiation in rat pheochromocytoma ( PC12) cells suggests potential differences between LD and lidocaine hydrochloride at the cellular level indicating an entirely different mechanism of action. Taken together these results suggest that the unique physiochemical properties of ILs in general, may confer a novel effect for the bioactivity of an API due to (at least) slow-release properties in addition to novel delivery mechanisms.