Marine-Inspired Synergistic Adhesion Enables Highly Efficient and Atraumatic Macromolecular Transdermal Delivery on Dynamic Skin

Abstract Effective transdermal drug delivery (TDD) demands both the ability to bypass the stratum corneum (ST) and the robustness to sustain delivery efficiency under real-life conditions. Despite advances in nanocarriers, microneedles, and electrostimulation, many TDDS strategies face limitations due to cytotoxicity, invasiveness, device dependence, and poor performance for large molecules in real-world conditions. In this study, we present a marine-inspired TDDS patch (PDA@SC) that integrates adhesion strategies from marine organisms to achieve stable skin attachment and atraumatic macromolecular delivery, even on dynamic skin surfaces. The suction-cup (SC) structure, inspired by octopus’ suckers, generates negative pressure upon preload-induced deformation, promoting temporary mechanical modulation for nanolevel control of the ST barrier and enhancing drug delivery without external power. Simultaneously, the mussel-inspired polydopamine (PDA) coating modifies hydrophobic surfaces into high surface energy interfaces capable of chemical bonding, thereby ensuring intimate adhesion and minimizing drug leakage. Experimental findings confirmed that the delivery of the high molecular weight compound was enhanced on deformed skin, showing a 600% improvement compared to conventional topical application. In addition, preliminary human evaluation demonstrated that PDA@SC effectively improved key dermatological parameters. Collectively, these results highlight the potential of PDA@SC as a platform that can drive technological progress in wearable therapeutics and cosmetics.