One Injection Could Keep Osteoarthritis Drugs Working for Weeks

Scientists at the University at Buffalo have developed an injectable hydrogel designed to keep osteoarthritis treatments working inside the joint for much longer than a conventional injection. Once injected, the material changes from a liquid into a smooth, lubricating semisolid depot at body temperature, and can remain in the joint for several weeks while gradually releasing drug-loaded nanocarriers.

Osteoarthritis is one of the world's leading causes of chronic pain and disability. Treatments delivered directly into the joint, including analgesics, corticosteroids and viscosupplements, can ease symptoms, but their effects are often short-lived and do not consistently slow the disease's progression. One obstacle is that small-molecule drugs and biologics are quickly cleared from the joint's synovial fluid; researchers also struggle to deliver hydrophobic, or water-repelling, drugs at concentrations high enough to work without raising drug exposure across the rest of the body.

The Buffalo team's hydrogel begins as a liquid, so it can be delivered through a minimally invasive injection, then rapidly turns into a lubricious semisolid at body temperature that acts as a local drug reservoir. It combines a biocompatible polymer matrix with drug-loaded nanocarriers designed to carry high amounts of poorly soluble therapeutic compounds. Once inside the joint, the compounds are released gradually through diffusion and the slow relaxation of the hydrogel matrix, providing controlled exposure over multiple weeks rather than a rapid disappearance from the joint. The researchers validated the approach using a SIRT6 activator, a compound that switches on a specific gene-regulating protein, and say the platform can be adapted to carry other hydrophobic disease-modifying compounds.

Because it also functions as a viscosupplement, the material can improve joint lubrication while delivering its therapeutic payload, and it was designed with disease modification in mind — potentially targeting chronic inflammation and cellular senescence, the process by which aging cells stop dividing, rather than pain relief alone. The researchers say a longer therapeutic window could reduce how often patients need invasive joint injections while lowering the risk of side effects elsewhere in the body.

The primary intended application is knee osteoarthritis, but the researchers say the same platform could potentially be adapted for post-traumatic osteoarthritis, intervertebral disc degeneration, rotator cuff degeneration, and the localized delivery of other hydrophobic drug candidates.