Gel to Fight Rheumatoid Arthritis

Rheumatoid arthritis (RA) is a long-term, autoimmune disease that causes inflammation and deformity of the joints – affecting close to 1% of the world’s population. While many researchers are focused on trying to understand better the biology of how RA begins, other scientists are developing improved technologies to alleviate the debilitating symptoms associated with the disease. To that end, IBS scientists at the Center for Self-Assembly and Complexity, within the Institute for Basic Science (IBS), invented a hydrogel to fight RA and other diseases.  The jelly-like material could be used to absorb extra fluids in swelling joints and release drugs.

Findings from the new study – published in Advanced Materials in an article entitled “Therapeutic-Gas-Responsive Hydrogel” – could be used to absorb extra fluids in swelling joints and release drugs. For RA, the body’s immune system attacks the soft tissue of the joints, leading to an accumulation of synovial fluid. While this clear fluid lubricates and nourishes the joints, its excess causes swelling and pain. Prevention of this swelling has been the therapeutic target for inflammatory joint disorders for many years.

Immune cells at the inflamed joints are the predominant source of nitric oxide (NO), a gas with various physiological functions. Current RA treatments are based on anti-inflammatory drugs that relieve pain and inflammation, but IBS scientists tried a more challenging approach by targeting NO itself. NO is a transient gas that stays in circulation for less than 10 seconds before binding to other molecules.

“Nitric oxide is like a double-edged sword. It regulates inflammation and protects our body by killing external pathogens,” explained senior study investigator Won Jong Kim, Ph.D., a group leader at IBS. “However, when in excess, it is toxic and may cause RA, as well as other autoimmune diseases, cardiovascular diseases, and cancer.”

The research team developed a gel responsive to such fugitive molecules, using acrylamide as a base material and a new crosslinker to keep it in place. Unlike the monomeric form, polymeric acrylamide hydrogel has little toxicity and can contain a large amount of water. Also, the crosslinking agent (NOCCL) forms bridges between the acrylamide molecules creating a net, which can trap drug molecules inside. When NO cleaves the NOCCL bridges, the gel changes its structure, frees the drug, and absorbs the new liquid.

“This study represents the first therapeutic-gas (i.e., NO)-responsive hydrogel by incorporating a NO-cleavable crosslinker. The hydrogel is rapidly swollen in response to NO, and not to other gases,” the authors wrote. “Furthermore, the NO-responsive gel is converted to enzyme-responsive gels by cascade reactions from an enzyme to NO production for which the NO precursor is a substrate of the enzyme. The application of the hydrogel as a NO-responsive drug-delivery system is proved here by revealing effective protein drug release by NO infusion, and the hydrogel is also shown to be swollen by the NO secreted from the cultured cells. The NO-responsive hydrogel may prove useful in many applications, for example, drug-delivery vehicles, inflammation modulators, and as a tissue scaffold.”

Although this is a preliminary study, the team confirmed that NOCCL crosslinking agent could selectively and sensitively react with NO. The scientists are now working on a nano-sized hydrogel in an RA mouse model. Moreover, these types of hydrogels could be useful for other diseases characterized by overexpression of NO, or maybe even as environmental sensors, since NO is also a polluting gas emitted in vehicle exhaust.