Dose–Response Relationship and Threshold Drug Dosage Identification for a Novel Hybrid Mechanical-Thrombolytic System with an Ultra-Low Dose Patch

Introduction Ischemic stroke treatment has advanced in the last two decades and intravenous thrombolysis is now considered the standard of care for selected patients. Recanalization can also be achieved by mechanical endovascular treatment for patients with large vessel occlusions. Complicating treatment-related symptomatic intracerebral hemorrhage and prolonged needle-to-recanalization times have been identified as major determinants of poor three-month functional outcomes. A hybrid mechanical-thrombolytic system with a patch imbued with an ultra-low dose of thrombolytic agents loaded onto a stent-retriever has been developed. Methods In this study, the in situ dose–response relationship of the thrombolytic patch imbued with up to 1000 IU of urokinase plasminogen activator (uPA) was quantified using Raman spectroscopy. Results Thrombi of up to 400 μ m thickness dissolved within 15 min when patches imbued with