A scientific team has designed a charged molecule that improved the delivery of osteoarthritis drugs to knee joint cartilage in rodent models of the debilitating joint disorder. Their approach "offers considerable promise" as a potential therapy that could address a major unmet clinical need in osteoarthritis treatment, notes Christopher Evans in a related Focus. Osteoarthritis impacts 200 million people globally and is characterized by the degeneration of joint cartilage, which leads to pain, inflammation and poorer quality of life for patients. Current treatments can manage symptoms as they worsen, but they cannot alter the course of the disease. What's more, many drug candidates fail in clinical trials for two reasons: the drugs are cleared from the joints before they can exert their effects, and they cannot efficiently penetrate the thick cartilage tissue that surrounds cartilage-producing cells (or chondrocytes). Brett Geiger and colleagues sought to overcome these barriers by engineering a "nanocarrier" - a very small molecule used to transport substances. The nanocarrier, called a dendrimer, has a positively charged surface that effectively binds to negatively charged cartilage tissue, allowing for deeper tissue penetration and a longer half-life in joint spaces. The researchers attached a cartilage growth-supporting factor named IGF-1 to their dendrimer and found that injections of the compound could penetrate cartilage from cows - similar in thickness to human cartilage - within two days. In rat models of osteoarthritis, a single injection of dendrimer-IGF-1 safely restored cartilage and bone integrity more effectively than IGF-1 administered without a nanocarrier, and reduced the width of cartilage degeneration in damaged rat knees by 60%. Geiger et al. say that their technology should be further investigated in large animal models before being tested in clinical trials.
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Science Translational Medicine