A multifunctional IL@MOF composite-based hydrogel for enhanced transdermal drug delivery of 5-fluorouracil

Advances in biomaterial-based transdermal drug delivery systems (TDDSs) are unlocking new possibilities for cancer therapy by enhancing skin permeability and enabling sustained drug release while minimizing systemic side effects. In this study, we developed a multifunctional hydrogel platform by encapsulating varying ratios of ionic liquids (ILs) into the micropores of judiciously selected metal-organic frameworks (MOFs), aiming to improve drug loading and delivery performance. Specifically, we utilized the [TMG][Ol] IL, UiO-66-NH₂ MOF, and carboxymethyl cellulose sodium salt to fabricate a synergistic composite hydrogel. The resulting system demonstrated outstanding thermal stability, mechanical strength, adhesiveness, self-healing properties, and spreadability-key attributes for efficient TDDS applications. Biocompatibility assessments using HaCaT cells showed ∼90% cell viability, confirming its cytocompatibility. Composite hydrogels prepared with [TMG][Ol]@UiO-66-NH₂ at ratios of 0.1 : 1 (G1) and 0.25 : 1 (G2) exhibited high drug-loading capacities of 671 mM and 397.8 mM for 5-fluorouracil (5-FU), respectively. <i>In vitro</i> transdermal drug penetration over 48 hours reached 76.4% for G1 and 82.7% for G2. Furthermore, cytotoxicity studies on A431 (epidermoid carcinoma) and MCF-7 (breast cancer) cancer cell lines confirmed the therapeutic potential of the drug-loaded hydrogels. Overall, the biocompatible [TMG][Ol]@UiO-66-NH₂-based hydrogel system offers a promising strategy for the transdermal delivery of hydrophilic anticancer agents, supporting its potential for future clinical translation in cancer therapy.