Tunable Deep Eutectic Solvent-Polymer Eutectogels for Controlled and Transdermal Drug Delivery

Deep eutectic solvents (DESs) and their gelled counterparts, known as eutectogels, have emerged as versatile drug delivery platforms because of their tunable physicochemical properties, high drug-solubilizing capacity, and ability to support controlled therapeutic release. Their ability to exhibit tunable physicochemical properties, together with their high solvation capacity, has attracted growing translational interest; however, their biocompatibility and safety profiles are increasingly recognized as formulation-dependent rather than inherent characteristics. Current evidence indicates that the safety of eutectogels depends primarily on the chemical composition of the deep eutectic solvent, concentration, exposure duration, and route of administration, rather than on an intrinsic property of all formulations. This review critically evaluates recent advances in the design of deep eutectic solvent-polymer eutectogels, focusing on solvent composition, gelation strategies, polymer selection, drug loading, release mechanisms, physicochemical characterization, transdermal delivery, and emerging biomedical applications. The current literature is dominated by studies involving transdermal drug delivery and wound-healing applications. Despite consistent improvements in drug solubilization and loading capacity achieved through modulation of deep eutectic solvent polarity and extensive hydrogen-bonding networks, the extent of these improvements remains highly dependent on solvent composition, temperature, and experimental conditions. Furthermore, eutectogels utilize strong intermolecular interactions to reduce molecular diffusion, thereby enabling sustained controlled drug release. Numerous studies have demonstrated improved skin permeation, thermal stability, mechanical performance, and protection of labile compounds compared with conventional hydrogels and ionogels. However, these advantages are formulation-dependent, and the biological compatibility and safety of eutectogels should be evaluated on a case-by-case basis, depending on their composition and exposure conditions. Despite encouraging preclinical findings, clinical translation remains limited by formulation heterogeneity, incomplete long-term safety evaluation, insufficient pharmacokinetic evidence, uncertainties regarding dilution stability under physiological conditions, and challenges associated with large-scale manufacturing. Addressing these limitations will facilitate the rational development and clinical translation of eutectogel-based drug delivery systems. DOI:10.2174/0122103031499423261102105051