Ionic Liquid-Enabled Drug Delivery Systems: Benefits, Limitations, and Future Perspectives

ILs have emerged as versatile formulation components in DDS due to their tunable physicochemical properties and ability to modulate biomolecular and interfacial interactions. This review examines IL-enabled DDS strategies across major delivery platforms, including nanocarrier-based systems, microtechnology-assisted devices, and biomacromolecule formulations, with emphasis on formulation design principles rather than administration route. We discuss how ILs enhance API solubility, stability, permeability, and formulation flexibility through API-IL complex formation and controlled membrane interactions and relate mechanistic insights into IL-membrane interactions to both delivery performance and safety via structure-activity relationships. Current limitations, including toxicity concerns, lack of standardized evaluation criteria, scalability challenges, and regulatory ambiguity, are critically assessed. Overall, this review positions ILs as formulation-enabling materials rather than standalone therapeutics and underscores the importance of rational design, standardized assessment, and early regulatory alignment for advancing IL-enabled DDS toward clinical translation.