Ionic Liquid‐Mediated Delivery of Ruxolitinib to Skin Using an Adhesive Topical Hydrogel System

Abstract Delivery of many drug types to the skin is prohibited by the stratum corneum, and drugs that can penetrate the epidermal barrier (e.g., small, nonpolar molecules) often have limited permeation in the dermis. Ionic liquids (ILs) are well‐known penetration enhancers, yet, achieving sustained, controlled drug release from ILs alone remains a significant challenge. Herein, ILs are incorporated into a removable, phenolic‐functionalized tissue‐adhesive hydrogel system for the treatment of atopic dermatitis. The hydrogel, enriched with galloyl groups from plant polyphenols, provides robust skin adhesion, effectively securing IL and ruxolitinib (Janus kinase (JAK) 1/2 inhibitor)‐loaded nanoparticles at the target site and enabling sustained delivery of the IL‐carried ruxolitinib into the dermis. The IL choline trans‐2‐butenoic acid (CA2BE) 1:1 can be embedded within the adhesive hydrogel without compromising its mechanical properties or inflaming macrophages. Importantly, the IL‐mediated transport of drug into the skin causes a significant increase in ruxolitinib accumulation within the dermis, surpassing that of a clinical ointment analog. By combining efficient skin permeation, controlled release, and strong adhesion, this multifunctional platform offers significant potential for topical drug delivery across a range of skin disorders, extending beyond atopic dermatitis.