Stepped Octopus-Inspired Architecture Microneedles for Pulmonary Embolism Prevention.

Pulmonary embolism (PE) is an acute thrombotic condition marked by pulmonary artery obstruction and high mortality. Current clinical management primarily depends on anticoagulants. Traditional oral and injectable formulations are hindered by delayed onset, low patient compliance, and side effects. Microneedles (MNs)-based transdermal delivery has emerged as a minimally invasive approach for the treatment of pulmonary embolism (PE). However, inadequate skin adhesion and low drug bioavailability continue to pose the therapeutic efficacy and convenience of anticoagulant MNs. To overcome these challenges, an innovative stepped octopus-inspired architecture microneedles patch (Step-OIAMNs) with high adhesion and high drug delivery efficiency was proposed here. Hyaluronic acid (HA) tip, loaded with recombinant hirudin, was positioned at the center of the methyl vinyl ether-co-maleic anhydride (PVM/MA) groove, where negative pressure was generated during application. The strong adhesion of the microneedle patch, achieved through negative pressure (~35.54 kPa), effectively improves drug delivery efficiency by counteracting the skin's natural rebound. Experimental results demonstrate that Step-OIAMNs not only significantly enhance transdermal drug permeation rates and blood drug concentration levels, but also exhibit excellent anticoagulant effects. In a murine acute PE model, Step-MN effectively suppressed thrombus formation and increased survival rates to 80%.