(122d) Evaluation of Ammonium-Based Ionic Liquids As Novel Chemical Permeation Enhancers for Transdermal Drug Delivery

Room temperature ionic liquids (ILs) are gaining growing interests in the area of transdermal drug delivery research thanks to several experimental evidence that they can enhance the permeation of macromolecules across the skin barrier^1,2,3,4. By definition, ILs are salts governed by ionic interactions as opposed to conventional chemical permeation enhancers which are molecular liquids. ILs are ideal candidates for transdermal permeation enhancement due to their low volatility, high recyclability and what’s more important, high tunability. Despite their vast parameter space available to synthesize and explore, our current knowledge of ILs is limited to a few specific ones⁴. In this talk, we aim to investigate the fundamental difference between ILs and conventional chemical enhancers in terms of skin permeation and provide a general guideline to future studies in this area.

Fourier-transform infrared (FTIR) spectroscopy has been shown as a powerful tool to examine solvent-skin interactions which significantly influence the permeability of drugs in transdermal applications. By comparing the FTIR spectra of 40 conventional chemical permeation enhancers and 40 novel ILs, we demonstrate superior performance of ILs in terms of high permeation enhancement and low irritation potential. This general observation can be explained by the fundamental difference between ILs and their molecular counterparts: polar interactions contribute to a significant portion of the cohesive energy density in ILs due to their ionic nature as compared to covalent materials. This property is preferable when a chemical enhancer acts to extract skin lipids and therefore increases drug permeability. While the search for molecular liquids with improved permeation performance has reached a bottleneck, our investigation of ILs as a novel class of permeation enhancers opens up new opportunities for transdermal drug delivery applications.

1. Qi, Q. M., & Mitragotri, S. (2019). Mechanistic study of transdermal delivery of macromolecules assisted by ionic liquids. Journal of Controlled Release, 311-312, 162–169.
2. Tanner, Eden E. L., et al. “Design Principles of Ionic Liquids for Transdermal Drug Delivery.” Advanced Materials, vol. 31, no. 27, 2019, p. 1901103.
3. Tanner, E. E., Ibsen, K. N., & Mitragotri, S. (2018). Transdermal insulin delivery using choline-based ionic liquids (CAGE). Journal of Controlled Release, 286, 137-144.
4. Ibsen, K. N., Ma, H., Banerjee, A., Tanner, E. E., Nangia, S., & Mitragotri, S. (2018). Mechanism of Antibacterial Activity of Choline-Based Ionic Liquids (CAGE). ACS Biomaterials Science & Engineering, 4(7), 2370-2379.