Supramolecular eutectogel based on THDESs as a skin penetrating carrier for effective transdermal delivery of hydrophobic drug curcumin

Therapeutic hydrophobic deep eutectic solvents (THDESs) are an emerging class of eutectic mixtures gaining significant attention in the biomedical field. Solidifying these THDESs into bioactive eutectogels broadens their application in transdermal drug delivery (TDD). To showcase the potential of these sustainable materials, we have developed a supramolecular eutectogel within THDESs. The investigated eutectogels were formed by dissolving pharmaceutically active compounds, cetylpyridinium chloride (CPCl) and cetylpyridinium bromide (CPBr), in THDESs, which were formed by the interaction of menthol (Mth) with fatty acids (FAs) such as lauric acid (LA), palmitic acid (PA), and oleic acid (Ole) through hydrogen bonding. The resulting supramolecular eutectogels, which form solely via reversible noncovalent interactions in response to temperature, exhibit a sol-gel-sol transition, highlighting their reversible temperature responsiveness. Furthermore, these eutectogels remain stable at room temperature for approximately four months, with no alteration in their physical properties. Notably, the mechanical properties of these eutectogels vary according to the chain length of the FAs used to form the specific THDES, with longer chain lengths imparting greater mechanical strength, following the order (Mth + Ole-DES) MeOle > (Mth + PA-DES) MePA > (Mth + LA-DES) MeLA. These eutectogels also show excellent adhesive properties on various substrates, including skin. Moreover, they retain the bioactivity of the THDESs and enhance skin penetration, facilitating the delivery of the anticancer drug curcumin in an ex vivo goat skin model via a Franz diffusion cell. These eutectogels exemplify the relationship between the system's hydrophobicity and its influence on curcumin loading capacity and skin permeation ability, paving the way for the development of innovative therapeutic soft materials.