High Wet Skin Adhesion Pressure‐Sensitive Adhesives for Long‐Term Transdermal Drug Delivery: Amphiphilic Strategy Based on Water‐Triggered Dual Activation

ABSTRACT Transdermal patches based on pressure‐sensitive adhesives (PSAs) are widely used for the delivery of diverse drugs. However, most PSAs are difficult to adapt to the wet microenvironments of the skin (sweating, bathing, humidity), thereby exhibiting inadequate adhesiveness. Meanwhile, integrating pharmaceutical and adhesion requirements into a single platform remains a challenge. Herein, a novel amphiphilic PSA (PETH) was synthesized within a water‐triggered dual‐activation strategy. Upon water molecule triggering, dynamic migration and rearrangement of hydrophilic/hydrophobic segments enhance bulk energy dissipation. In addition, protonation of secondary amine groups activates electrostatic/hydrogen bonding interactions with negatively charged skin surfaces. The as‐prepared adhesive achieves high adhesion strength of up to 66.7 kPa on wet porcine skin, superior to most reported transdermal adhesives. Furthermore, the low T g value of the hydrophobic segment and the strong hydrogen‐bonding interactions of HEAA ensure excellent adhesion on dry skin (74.5 kPa). Moreover, the interaction between multiple hydrogen‐bonding and hydrophobic regions enables PETH to retain key advantages for pharmaceutical applications: significantly enhanced drug loading capacity (1.7–6 times that of 4098) and stable, efficient drug release rates (60%–93% within 24 h). This study provides a simple preparation strategy and theoretical basis for developing next‐generation transdermal PSAs.