Synthetic or lab-grown versions of inhibitors to the tissue-degrading enzymes have been used in clinical trials, but only in a non-targeted fashion. Patients receive them intravenously or orally, with the hope that the inhibitor molecules make their way to the heart.
"As you can imagine, this type of delivery can lead to off-target problems," Burdick said. "In other tissues where enzymes and inhibitors are in balance, these extra inhibitors can throw that balance off. This can cause the stiffening of joints, for example."
"That's where our approach came in," Purcell said. "We used injectable gels to deliver the inhibitors locally, rather than systemically. And to really fine-tune the targeting, the innovation with this material is that it releases the inhibitor in response to the activity level of the enzyme."
The material the researchers used is known as a hydrogel, which in this design are squishy networks of sugars that are useful in mimicking different tissue environments. By making the hydrogel out of naturally occurring sugars, the researchers were able to hold the inhibitors within the hydrogel.
"We borrowed the way this specific inhibitor is localized and retained in normal tissues," Purcell said. "The inhibitors are physically held within the gel by electrostatic interactions with these sugars."
"If we didn't include this chemistry," Burdick said, "our experiments showed that about 80 percent of the inhibitor is released within a few days. When you have these bonds, only about 20 percent of the inhibitor is released over the course of a few weeks.
|Contact: Evan Lerner|
University of Pennsylvania