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Nanoparticle Drug Delivery

Drs. Broome and Dixit

By Leslie Cantu

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 rest of their lives, and these drugs leave them vulnerable to serious side effects.

“In the current state of affairs, people are taking 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 has just been granted a patent for a method of delivering antirejection drugs directly to the transplanted organ. The scientists believe that targeting the drugs to the transplanted organ will allow the rest of the immune system to continue to guard against infection and disease.

Nadig was particularly affected by the death of a college-aged patient who succumbed to the antirejection 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.

“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.

As they tossed around ideas, they realized that organs often spend hours in transport after being removed from the donor. And what’s being done to the organs during that time? 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 after the transplant.”

So the group began working on an idea to bathe the donor organ in the antirejection drug rapamycin as it was en route to the destination hospital.

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.

While this research is still in preclinical trials, Nadig said that it could be paradigm shifting. “It’s really the next era of transplant,” he said.