Gel offers an arthritis flare-responsive drug delivery system

Intra-articular injections may be superseded by an injectable gel that acts as a reservoir of drug which is only released in response to arthritis flares, US researchers say.

Scientists at Brigham and Women’s Hospital in Boston made the claim after investigating a hydrogel product that can be loaded with arthritis drugs that are released in response to inflammatory enzymes.

In proof of concept studies they have shown the gel can be injected into an inflamed joint to release a steroid in response to disease flares, rather than continually at a steady rate.

Reporting their development in Nature Communications, they describe how they selected the gel known as TG18, made from triglycerol monostearate, after screening FDA-listed available compounds that have the ability to encapsulate drugs and release them in response to breakdown by inflammatory enzymes.

In an animal study they loaded the TG-18 hydrogel with triamcinolone acetonide and injected into the joints of mice with arthritic disease.

“A single dose of [triamcinolone]-loaded hydrogel but not the equivalent dose of local- injected free triamcinolone reduced arthritis activity in the injected paw,” they noted.

They then repeated the experiment in laboratory models of human inflammation, using synovial fluid from human volunteers with rheumatoid arthritis.

“Strikingly, synovial fluid from human RA joints but not from healthy human joints significantly increased the cumulative triamcinolone release,” they said.

The TG18 hydrogel was a versatile platform that could be used to encapsulate a wide range of agents for arthritic joints, and was not limited to a single drug, they added.

“We have developed an arthritis flare-responsive drug delivery platform for on-demand intra-articular release of therapeutics. This system has the potential to provide the optimal amount of a therapeutic at a time when it is needed, thereby maximising therapeutic efficacy and prolonging the duration of the therapeutic benefit,” the researchers concluded.

“Local therapy could be a viable treatment option for patients with only one or a few inflamed joints, said co-author Dr Joerg Ermann, a rheumatologist in the hospital’s Division of Rheumatology, Immunology and Allergy.

“Moreover, if a patient is already on a systemic drug but is experiencing a flare in a limited number of joints, we could specifically treat these joints rather than switching systemic therapy or adding another systemic drug. Having this option would substantially increase our ability to successfully manage arthritis flares in the clinic.

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