Abstract 14336: Development of the New Drug Delivery System With Ultrasound for Coronary Thrombolysis
Background; Thrombolysis has the advantage of universal availability and rapidity compared to percutaneous coronary intervention. However, in thrombolysis, there are several disadvantages such as the low reperfusion rate and the occurrence of hemorrhagic complications. We have already reported that ultrasound (US) accelerates thrombolysis in rabbit arterial thrombosis model. Therefore, we developed the drug delivery system (DDS) regulated by US for thrombolysis for the purpose of improving disadvantages in thrombolysis, and tested the efficacy of our DDS in thrombolysis with the swine model of acute coronary syndrome (ACS).
Methods and Results; We generated the nanoparticle 100 to 150nm in diameter by combining tissue plasminogen activator (tPA), basic gelatin, and zinc acetate in phosphate buffered saline (0.5mg/ml, 10mg/ml, and 5mM, respectively). Fibrin plate method revealed that tPA activity of the nanoparticle was reduced by 55% compared to the same dose of tPA, and was recovered completely by 5 minutes-application of US (1.0MHz, 1.0W/cm2) in vitro. Next, we generated the transthoracic US device (1.0MHz, 1.0W/cm2) (TUS) for the application to the swine ACS model. Chromozym tPA assay revealed that plasma tPA concentration was reduced by 75% by nanoparticle, and was recovered almost completely at left circumflex coronary artery (LCx) but not at femoral artery by 5 minutes-application of TUS. We performed the balloon injury of LCx with distal balloon protection to induce thrombotic occlusion of LCx in 28 swines. The swines were devided into three groups: tPA (55,000 units/kg, iv) only group (n=10), tPA+TUS group (n=10), and DDS (nanoparticle containing 55,000 units/kg tPA, iv, +TUS) group (n=8). The rate of TIMI grade over 2 at 30 minutes was significantly higher in the DDS group (87.5%) than in the tPA only (10%) and tPA+TUS (40%) groups (p<0.01 vs tPA only group and p<0.05 vs tPA+TUS group). The mean TIMI grade flow at 30 minutes was significantly higher in the DDS group (2.4±0.3) than in the tPA only (0.4±0.2) and tPA+TUS (1.3±0.4) groups (p<0.01 vs tPA only group and p<0.05 vs tPA+TUS group).
Conclusions; The presented data suggest that our new DDS facilitates thrombolysis in ACS preventing hemorrhagic complications by reducing tPA activity.
- © 2010 by American Heart Association, Inc.