Researchers at the Harvard-affiliated Brigham and Women’s Hospital have developed a disease-responsive hydrogel for anti-inflammatory drug delivery. The hydrogel could be injected into joints in patients with inflammatory arthritis for long-term local treatment. The gel breaks down in response to enzymes that are increased in an inflamed joint during an arthritis flare, meaning that it could provide anti-inflammatory treatment directly in response to disease severity, at the place it is most needed.
Arthritis flares, during which symptoms of inflammatory arthritis get significantly worse, are often unpredictable, and make managing symptoms a challenge for arthritis patients. However, a research group at the Brigham and Women’s Hospital recognized that arthritis flares could be an opportunity for responsive, local therapy in inflamed joints.
“Arthritis represents a huge unmet clinical need,” said Jeff Karp, a researcher involved in the study. “Although new therapeutics have been developed, many have had systemic, toxic effects. We wanted to design a delivery system that could be efficient, deliver drugs locally and release drugs in response to inflammation.”
To make the hydrogel, the research team used a self-assembling compound called triglycerol monostearate (TG-18) from the FDA’s “generally recognized as safe” list. When present as a suspension, the hydrogel is liquid enough to be injected into an arthritic joint but can self-assemble to form a flexible and fibrous gel structure.
For this study, the researchers loaded the hydrogel with a model drug compound to investigate drug release, but they could also potentially load various anti-inflammatory compounds for a therapeutic version of the hydrogel.
“The hydrogel is designed so that drug release is triggered by the activity of specific, arthritis-related enzymes that are increased during flares,” said Nitin Joshi, another researcher involved in the study. “To test the TG-18 hydrogel, we exposed the gel to several different kinds of environments mimicking conditions in arthritic joints.”
The concept relies on the action of inflammatory enzymes present in arthritic joints during flares to degrade the hydrogel in a controlled manner, allowing the drug to be released in response to the severity of the flare. When the research team incubated the gel with synovial fluid from a healthy human joint, it released very little drug. However, in synovial fluid from an arthritic joint there was significant drug release, which could be repeated several times by re-exposing the gel to more inflammatory synovial fluid to mimic arthritic flares.
In a mouse model of inflammatory arthritis, the hydrogel released more drug in response to increased disease severity and helped to reduce swelling, showing that the therapy has clinical potential.
Study in journal Nature Communications: Towards an arthritis flare-responsive drug delivery system…