Functional ionic liquids for enhanced transdermal drug delivery: Recent advances and future perspectives

Ionic liquids (ILs) have emerged as a versatile and transformative class of materials in pharmaceutical sciences due to their unique physicochemical tunability, high solubilization capacity, and exceptional ability to modulate biological barriers. In recent years, increasing attention has been devoted to the application of ILs in transdermal drug delivery, particularly for the treatment of skin diseases, where conventional formulations often fail due to poor drug solubility, limited skin penetration, and low therapeutic efficiency. This review systematically summarizes recent advances in IL-based transdermal drug delivery systems, with a particular focus on functional or active pharmaceutical ingredient-ionic liquids (API-ILs). We discuss the fundamental design principles of ILs, including ion selection, structure-property relationships, and safety considerations, and highlight how rational molecular engineering enables precise control over permeability, solubility, and biocompatibility. Special emphasis is placed on IL-enabled delivery platforms, such as ionogels, microemulsions, microneedles, and nanocarriers, which collectively demonstrate superior drug-loading capacity, enhanced transdermal transport, and improved therapeutic outcomes. Furthermore, we critically analyze the biological safety, regulatory challenges, and translational barriers associated with IL-based formulations. Finally, emerging trends including AI-assisted IL design, stimuli-responsive systems, and integrated drug-carrier architectures are discussed as promising directions for future development. Overall, this review provides a comprehensive and forward-looking perspective on functional ionic liquid-based strategies for transdermal drug delivery and highlights their potential to reshape the treatment paradigm for dermatological diseases.