Title: Enhancing Transdermal Protein Delivery with Antimicrobial Ionic Liquids

Advisor: Patrick Daugherty

Abstract: 

Systemic delivery of macromolecules is most commonly done by injection, which can cause pain, dosing errors in inexperienced hands, and infection. A transdermal route is a compelling alternative due to its rich vasculature, but the outer layer of the skin represents a formidable barrier. Most methods available to increase skin permeability also cause significant damage; this research investigated ionic liquids (ILs) for their potential as low-irritation transdermal penetration enhancers. Best known as “green” solvents in the chemical industry, ILs are molten salts, usually with a bulky cation and smaller anion. With innate antimicrobial properties and excellent solvating properties, they are ideal candidates for transdermal delivery applications. This work demonstrated that a Choline And GEranic acid (CAGE) IL enabled the penetration of several proteins of varying size into skin by altering the lipid layers in the outermost skin layer, the stratum corneum. This same IL also increased the transport of insulin across the intestinal wall, a key challenge of oral drug delivery. Varying the ion ratios in CAGE resulted in varying degrees of skin permeability, irritation, and antimicrobial activity, demonstrating that simple tuning methods can be used to optimize CAGE properties for healthcare applications.