Institute of Applied Physics, University of Tsukuba, Tsukuba, Ibaraki 305-8573, Japan.
J Phys Chem B. 2010 Oct 28;114(42):13455-62. doi: 10.1021/jp101909a.
The poor aqueous solubility of drug substances hampers their broader applications. This paper describes a de novo strategy to increase the aqueous solubility of drug substances using an arginine-assisted solubilization system (AASS) with alkyl gallates as model drug substances. Solubility experiments of alkyl gallates showed that arginine greatly increases the aqueous solubility of different alkyl gallates, whose aqueous solubilities differ widely. In contrast, lysine showed marginal effects on alkyl gallates solubility. Molecular dynamic simulation indicated a greater interaction of arginine with alkyl gallates than that of lysine, which reflects favorable interaction between the guanidinium group of arginine and the aromatic ring of alkyl gallates. Such interaction apparently disrupts association of alkyl gallate molecules, leading to solubilization. These results indicate AASS as a promising approach to solubilize poorly soluble drug substances containing aromatic ring structures.
药物的水溶性差会限制其更广泛的应用。本文描述了一种使用精氨酸辅助增溶体系（AASS）提高药物水溶性的全新策略，以烷基没食子酸盐作为模型药物。烷基没食子酸盐的溶解度实验表明，精氨酸能极大地提高不同烷基没食子酸盐的水溶性，而这些烷基没食子酸盐的水溶性差异很大。相比之下，赖氨酸对烷基没食子酸盐的溶解度影响不大。分子动力学模拟表明，精氨酸与烷基没食子酸盐的相互作用大于赖氨酸，这反映了精氨酸的胍基与烷基没食子酸盐的芳环之间的有利相互作用。这种相互作用显然破坏了烷基没食子酸盐分子的缔合，导致其溶解。这些结果表明 AASS 是一种很有前途的增溶方法，可用于溶解含有芳环结构的难溶性药物。
