A nanotechnology-based drug delivery system developed at UVA Health to save patients from repeated surgeries has proved to have unexpectedly long-lasting benefits in lab tests—a promising sign for its potential to help human patients.
The approach would allow surgeons to apply a paste of nanoparticles containing hydrogel on transplanted veins to prevent the formation of harmful blockages inside the veins. These blockages often force heart and dialysis patients to undergo repeated surgeries; some dialysis patients need seemingly endless procedures on both arms and then a leg or around their collarbone so that they can continue to receive their lifesaving treatment.
While UVA’s innovation, dubbed “Pericelle,” produced encouraging results in early testing, there have been questions about how long the benefits this form of drug delivery could last. Would this quick and easy procedure, performed during the initial vein surgery, continue to protect patients months later?
That was the hope, but even the UVA scientists were surprised by their latest results: Not only did Pericelle work at three months—when the applied drug supply ran out—but it continued to work at six months and was still working at nine months.
The scientists can’t fully explain the unexpectedly durable benefits. But they are excited about what it suggests for the potential of their technique.
“This is a big deal because the treatment could work much longer than we originally thought, far beyond what people would expect,” said researcher Lian-Wang Guo, Ph.D., who is developing the technique with UVA’s K. Craig Kent, MD. “It is so exciting that one treatment can prevent the harmful blockages for many months.”
A $5 billion health care drain
Kent, a vascular surgeon who also leads UVA Health, is well acquainted with the challenges associated with “revascularization” procedures. These procedures are used to treat cardiovascular disease by restoring needed blood flow—for example, a surgeon might move a vein from the leg to the heart for patients with heart failure.
The procedure is also used to create access points for patients who need dialysis. An artery and vein in the arm, for example, are often grafted together so that a patient’s blood can be removed from the body, cleansed and then returned. These dialysis connection points are called “arteriovenous fistulas,” or AVFs, and management of them in patients with end-stage renal disease is estimated to cost the U.S. health care system $5 billion every year.
The problem is that revascularizations often cause the very problem they’re trying to fix: inadequate blood flow. The surgery itself causes a buildup of cells in the blood vessels that chokes off the blood supply.
“Repeated surgeries for vascular access and revascularization are not just a major burden for patients—they represent an urgent, unmet need in medicine,” said Kent, UVA Health’s chief executive officer and UVA’s executive vice president for health affairs.
“The strain on patients’ lives and the health care system is immense, and innovative solutions like Pericelle offer an opportunity to change this paradigm. We desperately need alternatives that can deliver durable, long-term results.”
Kent, Guo and their collaborator Shaoqin Gong, Ph.D., at the University of Wisconsin-Madison, hope Pericelle could be the answer. Surgeons would apply the hydrogel paste on blood vessels to deliver a drug, rapamycin, that can prevent the growth of invasive cells.
The UVA scientists had hoped that the results of their latest research would defy conventional wisdom and show that the drug would have benefits even after the applied supply ran out in three months. Six months, they thought, would be great; but they were wowed to see it still working in lab rats at nine months.
While much more research will need to be done before the approach could be made available to patients, the scientists are encouraged by their latest milestone and optimistic about what lies ahead. This type of cutting-edge nanotechnology research will be a key pillar of UVA’s Paul and Diane Manning Institute of Biotechnology, now under construction at Fontaine Research Park in Charlottesville.
“If we can find a way to prevent the need for repeated surgeries, it will have a huge impact on patients’ lives,” said Guo, of the School of Medicine’s Department of Surgery and the Robert M. Berne Cardiovascular Research Center.
In parallel with their work on Pericelle, Guo and Kent are also developing another surgery-saving approach, called “epiNanopaint,” that would let surgeons “paint” nanoparticles on veins to prevent the veins from becoming clogged in the future.
The research team consisted of Takuro Shirasu, Go Urabe, Nisakorn Yodsanit, Yitao Huang, Ruosen Xie, Matthew S. Stratton, Matthew Joseph, Zhanpeng Zhang, Yuyuan Wang, Jing Li, Runze Tang, Lynn M. Marcho, Li Yin, Eric W. Kent, Kaijie Zhang, Ki Ho Park, Bowen Wang, Kent, Shaoqin Gong and Guo. The researchers have no financial interest in the work.
