Mechanistic study of transdermal delivery of macromolecules assisted by ionic liquids.

Transdermal delivery of large hydrophilic molecules is a long-standing challenge owing to the strong diffusive barrier properties of the skin. Using choline and geranic acid (CAGE) based ionic liquid (IL) as a delivery technology, we report a significant improvement of transdermal transport of dextrans of various molecular weights up to 150 kDa. In addition, it is the first time that we show CAGE decreased the size-dependence of transport and thus can be applied to a broad range of solutes. At the molecular scale, we conducted Fourier Transform Infrared (FTIR) spectroscopy studies which showed lipid extraction in the skin due to CAGE. Based on these experimental observations, we built a novel theoretical model that elucidates how CAGE-induced skin structural changes result in faster macromolecular diffusion for enhanced permeability. The fundamental understanding gained from this study demonstrates the potential of ionic liquids as an effective and noninvasive transdermal drug delivery method.