The outermost layer of human skin, the stratum corneum (SC), is composed of corneocyte cells embedded in a lipid matrix. The SC forms a highly effective barrier, preventing harmful agents from entering the body, but importantly is the interface with topical formulations and active pharmaceutical ingredients (APIs). Choline geranate (CAGE), a class of ionic liquid (IL), is of high interest due to its effective transdermal drug delivery and antimicrobial properties; however, the mechanism of penetration through membranes is not fully understood.

We have utilised a simplified, synthetic SC lipid mimic, which is an effective and controllable model for investigating the specific molecular interactions that underpin physical and structural changes induced by the application of topical formulations, such as CAGE. We show that the hydration of CAGE causes changes in its structural organisation from a simple lamellar structure to micellar assembly and, finally, an emulsion phase. The importance of the sterically hindered geranic acid groups was shown by the analysis and comparison of 3 analogues of CAGE.

Furthermore, we have also shown that CAGE causes significant disruption to the mesostructure of model skin lipids and membranes. These phase transitions and structural organisation have been investigated using several biophysical techniques, including differential scanning calorimetry, x-ray diffraction, solid-state (SS) NMR and light microscopy.

The outcome of this project has a significant impact on the topical formulations industry as well as our understanding of the complex structure of the body’s skin barrier. Understanding these physical interactions is critical to the design of effective topical formulations.