Multiple dynamic interaction-enabled eutectogel with strong tissue adhesion, mechanical strength and temperature tolerance for transdermal drug delivery: Double monodentate coordination and π-π interaction

The application of conventional hydrogels in transdermal drug delivery system (TDDS) is limited due to their inability to provide high adhesion and cohesive strength simultaneously. Additionally, hydrogels are vulnerable to temperature fluctuations, which can cause freezing or dehydration, leading to a loss of adhesion and cohesion, thereby failing to ensure steady drug delivery. In this study, taking inspiration from natural mussels and deep eutectic solvents (DES), we introduce the calcium ion-coordinated p-hydroxyphenyl methacrylate (HP-Ca2+) eutectogel utilizing choline chloride-ethylene glycol (ChCl-EG) DES as solvents, by virtue of coordination bond-enabled multiple dynamic interactions (MDI) to fully substitute conventional covalent crosslinking. This novel eutectogel exhibits remarkable properties that surpass those of conventional hydrogels applied in TDDS. These properties include exceptional stretchability (>1600 %), high tensile strength (>300 kPa), strong skin adhesion (>30 kPa), and excellent temperature tolerance (-25–60 °C). We have demonstrated that remarkable features of HP-Ca2+ eutectogel are achieved through MDI, specifically double monodentate coordination, strong π-π interaction, and double hydrogen bond, characterized by XPS, ITC and 2D NMR. The synergistic effects of MDI provide numerous non-covalent crosslinking sites, improving cohesive strength, and serving as an integrated platform for tailoring interfacial properties to enhance adhesion. Furthermore, the HP-Ca2+ eutectogel exhibits exceptional thermal stability and controlled release capabilities for transdermal drug delivery. Through comprehensive evaluations, the HP-Ca2+ eutectogel emerges as a highly effective solution for developing transdermal drug delivery patches.