Recent advances of ionic liquids for transdermal drug delivery systems

Pharmaceutical application of ionic liquids (ILs), which are commonly defined as salt compounds composed of ionic species and melt below 100℃, is an attractive research field in a drug delivery system (DDS). The solubilization ability for insoluble drug molecules is a promising property of ILs. In 2010, it was reported that acyclovir, a sparingly soluble drug, was dissolved in imidazolium-based ILs, and the IL-in-oil microemulsions enhanced the transdermal delivery of acyclovir. The transdermal delivery is the most studied DDS field using ILs and some hydrophobic ILs were confirmed as skin penetration enhancers due to its higher interaction with the hydrophobic skin surface barrier. Utilization of active pharmaceutical ingredients (API) as the ions of ILs is known as an alternative strategy of IL-based DDSs because the API-IL enables to tune their physical or chemical properties of ILs. To improve the transdermal delivery, drugs were robed with hydrophobic counter ions. Recently, biocompatibility has been regarded as one of the most important properties of ILs for the DDS application. Several biomolecule-derived ions such as choline and amino acids were reported to form ILs and the biocompatible ILs were used as a solvent for solubilizing poorly soluble drugs and skin penetration enhancers. These researches suggest that ILs would be a promising solvent for developing a novel DDS.