Development, Characterization, and Evaluation of CAGE-based Ionic Liquid Systems for Transdermal Delivery

Ionic liquids have recently gained remarkable recognition for their applications within drug delivery, in particular their potential to enable cutaneous drug penetration and enhance drug permeation. In addition to enhancing barrier permeability, ionic liquids have excellent solvation properties, addressing the challenge of dissolving poorly soluble drugs. Due to the large asymmetry between the organic cations and anions, these functional salts remain liquid at room temperature. From an application perspective, ionic liquids provide a promising and highly tunable approach to serve multiple therapeutic areas. A biocompatible ionic liquid composed of choline and geranic acid (CAGE), in a stoichiometric ion ratio of 1:2, holds immense potential for transdermal delivery of a wide range of active pharmaceutical ingredients, including small molecules, peptides, proteins, and nucleic acids. This has a minimal impact on skin barrier function. Herein, we share our methods for the preparation, characterization, and evaluation of CAGE. Representative results are shown for CAGE characterization using NMR spectroscopy, differential scanning calorimetry, Karl-Fischer titration for water content analysis, and ex vivo barrier interaction studies on porcine skin.