SBIR-STTR Award

The overall goal of this project is to demonstrate the feasibility of using ultrasound to temporarily make vascular tissue more permeable and thereby deliver drug to the cells in the vessel wall (e.g. smooth muscle cells). EKOS has developed an ultrasound-catheter device for the transmural delivery of drugs and we are seeking to understand the mechanisms by which ultrasound can make tissue more permeable and thereby enhance transport of drugs and genes into target tissues and inside of cells. We propose the use of ultrasound to transiently disrupt cell membranes for delivery of drugs, proteins, and DNA. This non-chemical, non-viral, and minimally-invasive approach could provide a safe means for targeted cell uptake in the treatment of restenosis and other cardiovascular diseases. Despite compelling initial experiments, ultrasound-mediated cell permeabilization has been insufficiently characterized to rationally design protocols for applications. understanding the effects of ultrasound parameters on cells and reproducibly achieving those effects at different times and in different patients is essential to developing a clinical product. The specific aims are: 1. Determine the effect of acoustic parameters on molecular uptake and cell viability 2. Characterize the size and lifetime of membrane disruptions 3. Identify acoustic signals that correlate with membrane disruption threshold PROPOSED COMMERCIAL APPLICATION: Our product will be an ultrasound catheter device that actively delivers drug into the artery wall for the treatment of restenosis.

The goal of this project is to demonstrate the feasibility of using ultrasound to temporarily make vascular tissue and cell membranes more permeable to deliver drug to vessel walls. EKOS has developed an ultrasound-catheter device for transmural drug delivery that may be useful in the treatment of restenosis following balloon angioplasty. Local ultrasound enhanced drug delivery may increase the usefulness of drugs that are too toxic or expensive to deliver systemically. The results of Phase I demonstrated that ultrasound can make eukaryotic cells permeable for the uptake of exogenous materials. The permeability was correlated with aspects of the acoustic signature radiated by the cavitation field in the cell suspension during exposure. The aims of Phase II are to determine the effect of acoustic parameters on molecular uptake and cell viability in simple cell suspensions and more complex organized tissues and to develop a measure for the cavitation mediated permeability based on acoustic signature analysis. This measure will give a real time feedback predicting the bioeffects for optimizing therapy delivery. PROPOSED COMMERCIAL APPLICATION: The EKOS product will be an ultrasound catheter device that actively delivers drug into the artery wall for the treatment of restenosis.