SBIR-STTR Award

The broader impact/commercial potential of this Small Business Innovation Research (SBIR) Phase I project is to address the massive unmet need of peripheral arterial disease (PAD) which affects over 12 million Americans and results in over 65,000 amputations each year. This project will provide the proof of concept for a novel drug delivery technique that will improve the durability of procedures to restore blood flow in PAD patients. The result technology will help reduce the burden of disease while reducing the significant societal and health system costs caused by amputations. The proposed project will address the challenge of providing controlled drug dose to arteries of varying diameter and length. Peripheral arterial disease (PAD) patients have atherosclerotic lesions that are long and diffuse, requiring treatment to multiple sites with different vessel diameters and lengths. Existing drug delivery platforms require the use of multiple, expensive devices to treat these patients. This project will demonstrate that a single ultrasound-enhanced drug delivery catheter can provide drug delivery to different artery diameters and lengths, providing significant potential cost and time savings during endovascular procedures. In order apply the desired drug dose to arteries of varying size, real time imaging feedback will be used to adjust the treatment settings to compensate for changes in size. To achieve this goal, ex vivo swine arteries of different sizes will be treated under physiological flow conditions while varying the treatment parameters in order to determine the effect of vessel size on delivered drug dose. From this project, algorithms that can control drug dose to match varying artery diameter will be developed for future in vivo animal model studies.

This SBIR Phase II project will develop a drug delivery technology to address the unmet need of antiproliferative drug delivery below-the-knee. In the United States, there are 323,000 new critical limb ischemia (CLI) patients each year. CLI is the most severe stage of peripheral artery disease (PAD), atherosclerosis of the lower limbs. Ultimately, 40% of CLI patients will undergo lower limb amputation as a result of CLI, half of whom will then die within a year. Existing technologies have failed in these vessels, resulting in higher rates of patient amputation. This project will create a better intravascular drug delivery tool to treat PAD patients after angioplasty. This improved drug delivery will provide three key societal

Benefits:
1) reduced costs and greater efficiency when revascularizing the vessels of critical limb ischemia patients, 2) a reduction in healthcare costs by reducing repeat procedures, and 3) improved patient outcomes resulting from improved drug delivery achieved using image guidance. If successful, this technology may improve patient health while reducing treatment costs for millions of patients around the world. This will also improve understanding of what aspects of CLI treatment are most effective by offering the flexibility to vary different aspects of drug delivery. When completed, this project will enhance the understanding of intravascular drug delivery with ultrasound and microbubbles.This project will provide strong technical innovation through a new ultrasound drug delivery device and new methods to evaluate cardiovascular drug delivery devices. Using a combination of intravascular ultrasound and drug loaded microbubbles, this project will provide better localization of delivery with lower drug doses. This project will then evaluate the drug delivery platform using realistic models of human disease from donated tissue combined with routine techniques (histopathology) and more recent advances (microCT) to evaluate the effect of the disease on drug delivery. The core research objective of this project is to deliver paclitaxel to human diseased arteries with the new intravascular ultrasound and microbubble drug delivery platform. It is anticipated that this project will result in an improved drug uptake over the existing technologies in diseased arteries where drug uptake is poorest. The data and techniques from this project will be used to compel adoption among interventionalists and to validate the the drug delivery system as a tool to prevent amputations in CLI patients.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.