Smart supramolecular eutectogels-based deep eutectic solvent for pH- and thermo-responsive transdermal delivery of anticancer curcumin

Curcumin exhibits potent anticancer and antioxidant activities; however, its efficacy is hindered by poor solubility, instability, and low transdermal permeability. In this study, smart supramolecular eutectogels (Egel-1 and Egel-2) were designed as a dual pH- and thermo-responsive platform for the transdermal delivery of curcumin. The eutectogels, constructed using cetyltrimethylammonium bromide (CTAB)-based deep eutectic solvent systems, demonstrated outstanding multifunctionality with anti-drying properties of 112.1 ± 1.5% (Egel-2) and 104.3 ± 4.2% (Egel-1), encapsulation efficiencies of 66.24% and 56.33%, and positive zeta potentials of +31.27 ± 7.25 mV and + 21.30 ± 9.03 mV, respectively. In vitro degradation assays revealed accelerated degradation under mildly acidic conditions (pH 5.5), confirming pH-responsive behavior, while XRD confirmed the amorphization of curcumin upon encapsulation. Curcumin-loaded eutectogels exhibited a sustained and temperature-dependent release extending beyond 24 h under both physiological (pH 7.4) and acidic (pH 5.0) conditions. Furthermore, the eutectogels displayed enhanced curcumin stability–by 237-fold (Egel-1@Curcumin) and 135-fold (Egel-2@Curcumin)–and maintained structural integrity up to 75 °C. The DPPH assay indicated prolonged antioxidant activity, achieving complete inhibition of ∼99% after 150 min. These findings underscore the potential of CTAB-based supramolecular eutectogels as smart transdermal drug delivery systems (STDDSs) offering controlled release, superior stability, and improved therapeutic efficacy for curcumin and other hydrophobic agents.