High-performance adhesive eutectogel based on polyacrylate-carboxylated cellulose nanofibers double networks for efficient transdermal drug delivery.

Due to their poor ability to solubilize lipophilic drugs and insufficient skin adhesion, conventional hydrogels show limited application in transdermal drug delivery systems (TDDSs). Eutectogels are considered promising alternatives to hydrogels because of their excellent drug solubility, adhesion, and stability. This work reports the preparation of a high-performance double -network eutectogel using ChCl-urea deep eutectic solution as the solvent, poly (4-hydroxyphenyl methacrylate-co-acrylic acid-co-N-vinylpyrrolidone) and carboxylated cellulose nanofibers as first polymer network and second polymer network, respectively, and Zr4+ as a physical crosslinker. Compared to conventional hydrogels, the prepared eutectogel demonstrated superior performance in TDDS, including an excellent elongation rate (> 1400%), high tensile strength (0.89 MPa), strong skin adhesion (> 60 kPa), strong self-healing capacity, and outstanding stability across the temperature range of -20 to 60 °C due to the multiple hydrogen bond interactions and metal coordination. Meanwhile, owing to the enhanced drug solubilizing effects of DES solvents and acrylate polymers, eutectogel significantly enhanced flurbiprofen drug loading and demonstrated excellent therapeutic effects through in vivo pharmacodynamics experiments, highlighting its potential as an efficient platform to facilitate transdermal therapy for chronic diseases, including arthritis, offering an effective way to develop transdermal patches for low-solubility drugs.