(675f) Designing Ionic Solvents for Transdermal Delivery

Authors: 
Tanner, E. E. L., Harvard University
Mitragotri, S., Harvard University
The recent application of ionic solvents, including Ionic Liquids and Deep Eutectic Solvents, to the biomedical context has brought the non-invasive transdermal delivery of pharmaceuticals closer to clinical realization.[1,2]Choline and geranic acid based ionic liquids (CAGE) have shown excellent biocompatibility and the ability to carry large (ca. 6000 Da) molecules through to the dermis.[3,4]Systematic manipulation of the cation and anion reveals a molecular structure/function relationship, which enables the task specific design of ionic solvents for transdermal drug delivery. Using two model drugs of differing hydrophilicities, acarbose and ruxolitinib, and 16 ionic liquids of varying cations and anions, we examine the dependence of skin penetration on the chemical properties of ILs. This talk will elucidate the lessons learnt thus far on the role of stoichiometry and inter-ionic interactions in mediating transport, thus illustrating how delving into the chemistry of this solvent class can provide a straightforward, effective bioengineering design strategy in the use of ionic solvents in transdermal drug delivery applications.

[1] Agatemor C, Ibsen KN, Tanner EEL, Mitragotri S. Ionic liquids for addressing unmet needs in healthcare. Bioeng Transl Med 2018;3:7–25. doi:10.1002/btm2.10083.

[2] Monti D, Egiziano E, Burgalassi S, Chetoni P, Chiappe C, Sanzone A, et al. Ionic liquids as potential enhancers for transdermal drug delivery. Int J Pharm 2017;516:45–51. doi:10.1016/J.IJPHARM.2016.11.020.

[3] Zakrewsky M, Lovejoy KS, Kern TL, Miller TE, Le V, Nagy A, et al. Ionic liquids as a class of materials for transdermal delivery and pathogen neutralization. Proc Natl Acad Sci 2014;111:13313–8. doi:10.1073/pnas.1403995111.

[4] Banerjee A, Ibsen K, Iwao Y, Zakrewsky M, Mitragotri S. Transdermal Protein Delivery Using Choline and Geranate (CAGE) Deep Eutectic Solvent. Adv Healthc Mater 2017;6:1601411. doi:10.1002/adhm.201601411.