Eutectogel with superior adhesion and high drug loading for transdermal delivery of loxoprofen against arthritis induced in rats

Transdermal drug delivery represents an important therapeutic approach for arthritis. However, conventional hydrogels for transdermal drug delivery face several challenges, including insufficient adhesion, low drug-loading capacity for hydrophobic drugs, and poor environmental stability, which hinder their ability to meet clinical needs. In this study, a novel eutectogel was developed using poly(acrylic acid-co-4-hydroxyphenyl methacrylate-co-2-hydroxyethyl acrylate) as the network and zirconium ions as the crosslinking agent for high-performance transdermal drug delivery. The prepared eutectogel demonstrated excellent adhesion, mechanical strength, and environmental stability. The deep eutectic solvent and the polyacrylate network showed synergistic effects, leading to significant improvement of the solubility of loxoprofen in eutectogel. Infrared spectroscopy and molecular docking confirmed that the drug binds to the eutectogel via multiple hydrogen bonds, resulting in stable and controlled transdermal release. Furthermore, the eutectogel displayed excellent biocompatibility and distinct therapeutic efficacy against arthritis in animal studies. The eutectogel offers a novel transdermal drug delivery carrier for arthritis therapy, providing superior performance, a well-defined mechanism of action, and proven safety and efficacy.