MUSC researchers awarded patent on nanoparticle that delivers transplant drug

December 20, 2019
group photo
Drs. Suraj Dixit and Ann-Marie Broome brought the bioengineering and nanochemical experience to the group of four MUSC researchers who worked on the nanoparticle idea. Photos by Sarah Pack

Organ transplants have allowed hundreds of thousands of people in the United States to add years to their lives. But the procedure is far from perfect. Recipients must take antirejection drugs for the remainder of their lives, and these drugs leave them vulnerable to serious side effects.

“In the current state of affairs, people are taking these antirejection medications, which are going through their whole body,” said Satish Nadig, M.D., D.Phil., who holds the P.K. Baliga, M.D. Endowed Chair in Solid Organ Transplantation. “It’s preventing early rejection, which is great, but patients are also succumbing to heart disease, diabetes, infections, and failure of the organs that the drugs are supposed to be protecting, because they’re toxic to those organs as well.”

But the team of Nadig; bioengineer Ann-Marie Broome, Ph.D., M.B.A.; immunologist Carl Atkinson, Ph.D.; nanochemist Suraj Dixit, Ph.D.; and the MUSC Foundation for Research Development (FRD) has just been granted a patent for a method of delivering anti-rejection drugs directly to the transplanted organ. The scientists believe that targeting the drugs to the transplanted organ will allow the rest of the body’s immune system to keep its guard up, protecting against infection and disease.

The process of developing an invention and applying for a patent takes years. Broome recalls that she got a call “out of the blue” about four months after she joined MUSC in 2012. It was Nadig, who was about to join the faculty; he had heard that she was doing nanoparticle research.

Nadig had been particularly affected by the death of a college-aged patient who succumbed to the anti-rejection medication. He started thinking there must be a way to target transplanted organs in the same way oncologists target tumors. Broome was excited about the idea.

“It was a unique avenue for me because I was primarily studying cancerous diseases, not necessarily associated with surgical transplantation. It was exhilarating because it was a whole new field to explore,” she said.

Atkinson and Nadig walk down a hallway talking animatedly 
Drs. Carl Atkinson and Satish Nadig have collaborated on a number of projects.

They quickly pulled in Atkinson for his immunology expertise. Dixit was a postdoctoral fellow in Broome’s lab who had expertise in packaging and delivering nanoparticles to fight cancer. Initially, the group wanted to create a more focused path to deliver drugs directly to the transplanted organ after surgery. While that remains a goal, they realize there is a long regulatory path to reach it.

“The satisfaction and effectiveness of team science is that you come up with a lofty idea and then you delve down and think, where is the low hanging fruit that you can do quickly?” Broome said.

And as they tossed around ideas, they realized – organs often spend hours in transport after being removed from the donor. What’s being done during that time to prep the organ for transplant?

Answer: Not much.

“That’s a prime opportunity where not much is happening other than storage and delivery,” Broome said. “It gives us a chance to treat for events that we know are going to happen downstream, after the transplant occurs.”

"That’s a prime opportunity where not much is happening other than storage and delivery. It gives us a chance to treat for events that we know are going to happen downstream, after the transplant occurs."

Dr. Ann-Marie Broome

So the group began working on an idea to bathe the donor organ in the anti-rejection drug rapamycin as it was en route to the hospital where the transplant surgery would occur. Once they came up with the idea, it seemed that, surely, someone else would have already thought of it. But, Broome said, “With the assistance of FRD, we did an analysis on what was out there, and to our surprise, it hadn’t been done.”

Constructing the nanoparticle took quite a bit of work, Broome said. As the nanochemist, Dixit took the lead in figuring out the best elements to use to encapsulate the drug. The group then went a step further by developing a targeting system so the nanoparticle would head to the organ and then rupture upon contact with the endothelium, releasing the drug.

The group tested three ideas: letting the drug float freely in the perfusion solution, encapsulating the drug in a nanoparticle, and encapsulating the drug while also adding the targeting effect.

“We were very excited to see that packaging and targeting worked. In fact, we repeated many of the experiments multiple times because we could not believe our eyes,” Broome said.

Thanks to a Small Business Technology Transfer Grant from the National Institutes of Health National Institute of Biomedical Imaging and Bioengineering, the group is now conducting preclinical trials. If all goes well, the group can move on to clinical trials in humans, which could be “paradigm shifting,” Nadig said.

“It’s really the next era of transplant,” he said.