cientists have created a drug-loaded hydrogel that can be injected into a joint and respond in real time to an arthritis flare-up.
Biomedical engineer Jeff Karp and his colleagues at Brigham and Women’s Hospital in Boston tucked an arthritis drug, triamcinolone acetonide, inside a hydrogel that breaks down as inflammation in the knee joints of arthritic mice ramps up. Alivio Therapeutics — a biotech company co-founded by Karp — is working to use the technology on a range of inflammatory diseases.
STAT chatted with Karp about the work, published Tuesday in Nature Communications.
What problem did you set out to solve?
There’s been a big push to advance new therapeutics, but the majority have been pills, which means the drug is going to go everywhere throughout the body. And to get the concentration of an arthritis drug high enough in the affected joint, you need to deliver a pretty high concentration.
The next potential target is to deliver drugs locally by just injecting them into a joint. But the problem is the drugs are cleared fairly quickly, because there’s an efficient drainage system for the joint’s synovial fluid. The drugs don’t stay in the joint very long, so relief for a patient might only be a few weeks.
How does the hydrogel address those issues?
We developed a material that’s made of a small molecule. Each molecule stacks on top of one another to form a gel — it’s just a single molecule stacked over and over. And during that assembly, we can include arthritis drugs in the stack. That small molecule includes an enzyme-cleavable bond, which means it can be split by enzymes that are present during inflammation. So in the presence of a flare-up, the first molecule will break down, then the second, and so on. The concentration of the inflammation enzymes starts to go down [and cleaving slows].
How did you test it?
In a mouse model of arthritis, we saw that our material disassembled much more rapidly in higher levels of inflammation. The release of the drug was coordinated with the severity of the arthritis flare. We achieved significant reductions in the severity of the disease, and we showed we only needed a single dose to suppress the disease for the course of the animal study [approximately 30 days]. We’d now like to move to including biologics and move these studies to larger animals.