Fighting Life-Threatening Sepsis with Nanoparticles

Ryan Pearson, PhD, says custom-designed particles may do what medicines can’t.

Sometimes the body responds to infection with an overreaction, casting a storm of life-threatening inflammation called sepsis.

Sepsis can lead to tissue damage and organ failure and is the leading cause of death in hospitals in the United States. But sepsis is also very complicated and presents with different symptoms in different patients. When diagnosed with sepsis, patients are often treated with antibiotics to fight the underlying infection, while at the same time receiving fluids to stabilize organs and oxygen to improve breathing. Still, finding more effective tools to fight sepsis has proved to be very difficult.

Ryan Pearson, PhD, associate professor of pharmaceutical sciences and director of the Bio- and Nano-Technology Center at the University of Maryland School of Pharmacy, has been awarded a $3.4 million grant from the National Institutes of Health to move forward with a unique approach to defeating sepsis using nanoparticles. His approach is different because the custom-designed nanoparticles are not used to transport other drugs, but are themselves the treatment.

These drug-free nanoparticles are composed of biocompatible lactic and polylactic acid, which serve to change different aspects of a person’s immune response. In early tests, they’ve been shown to reduce proinflammatory responses without damaging key immune cells. They also work well with other antibiotics to improve the immune system’s ability to neutralize harmful bacteria causing infection.

Pearson’s interdisciplinary team includes co-principal investigator Lin Zou, MD, PhD, associate professor at the University of Maryland School of Medicine (UMSOM), and co-investigator Wei Chao, MD, PhD, FAHA, Anesthesiology Endowed Professor of Translational Research at UMSOM.

Questions

Are nanoparticles naturally occurring or are they man-made?

They can be prepared from either naturally derived materials or synthetic materials that we synthesize on our bench tops. Our lab is focused on nanoparticles that are in the size range between 10 to 500 nanometers most generally. And what's really neat about nanoparticles is that as you make materials that are smaller, they have these very unique characteristics where they can leverage different biological processes and modify them so that they can elicit a profound and robust therapeutic intervention.

How does your current research use nanoparticles?

My most recent NIH-funded R01 project is related to developing drug-free immunomodulatory nanoparticles to dampen severe inflammation and improve outcomes in sepsis. Now, sepsis, maybe you don't know, it has been shown to kill upwards of 1 in 5 individuals globally. So, that means that 20 percent of the global population will die of sepsis or sepsis-related causes. What we're trying to do in this case is to understand how we can develop new types of immunomodulatory therapies to enhance current standard of care treatments so that we can improve patient survival. And in the United States, what that means is that those 350,000 people that die every year of sepsis have a greater chance of living.

There is currently no FDA-approved sepsis therapy that improves patient survival, but are there other experimental drugs?

Unfortunately, many of these investigational drugs have not made it to the point where they can improve patient survival. Our nanoparticles are very simple and comprised of FDA-approved biomaterials to limit the regulatory hurdles to achieve FDA approval.
Nevertheless, there are still many steps that are moving, that are required in order to push our technology forward. And our lab, through this NIH funding, is working to close this translational gap and obtain additional data to support first-in-human clinical trials using our nanoparticle-based immunomodulatory therapy.