BioE PhD Proposal Presentation- Mónica B. Pérez Cuevas

Committee:

Mark Prausnitz, Ph.D. (Georgia Institute of Technology - CHBE) - Chair

Sven Behrens Ph.D. (Georgia Institute of Technology - CHBE)

Julie Champion Ph.D. (Georgia Institute of Technology - CHBE)

Saad Bhamla Ph.D. (Georgia Institute of Technology - CHBE)

M.G. Finn Ph.D. (Georgia Institute of Technology - CHEM)

"High-Throughput Synthesis of Liquid Salts for Enhanced Transdermal Drug Delivery"

The field of room temperature ionic liquids (ILs) and deep eutectic solvents (DESs), which are together referred to as liquid salts (LS), has emerged as a promising approach for the development of novel drug administration. Ionic liquids consist of bulky cation-anion combinations which render the salt unable to fuse to a solid state at room temperature. Deep eutectics consist of a mixture of anionic/cationic species and a hydrogen bond donor (HBD) which form a liquid at a temperature below the individual melting temperature of the constituent species. DESs are usually obtained by the combination of a quaternary ammonium salt with a metal salt or HBD. Both ILs and DESs have been shown to have interesting solvent properties, and could potentially replace the need for solvents in drug formulations by incorporating the active pharmaceutical ingredient (API) as a counter ion. Because the API is incorporated at higher concentrations than a typical drug solution (50% in the case of ILs), formulating hard-to-dissolve drugs as liquid salts could improve their pharmacokinetics, and the tunability associated with ion selection can aid in minimizing potential toxicity. Currently, the development of novel LS is limited by significant trial and error in the screening of suitable counterions. In this thesis, we will develop an automated high-throughput method for the synthesis of LS to study ion pair combinations that incorporate pharmaceutically relevant species and study counterion influence over their synthetic outcome. This project aims to characterize the physicochemical properties of the developed LSs and use these insights to generate guidelines for future LS design. Furthermore, we will evaluate the potential of the synthesized LSs for transdermal applications and evaluate a lead LS formulation in-vivo as proof of concept. This work has the potential to enhance the bioactivity of previously problematic drug candidates, and expand our knowledge on biocompatible LS design.