Intra-articular delivery of an indoleamine 2,3-dioxygenase galectin-3 fusion protein for osteoarthritis treatment in male Lewis rats.

Objective: Osteoarthritis (OA) is driven by low-grade inflammation, and controlling local inflammation may offer symptomatic relief. Here, we developed an indoleamine 2,3-dioxygenase and galectin-3 fusion protein (IDO-Gal3), where IDO increases the production of local anti-inflammatory metabolites and Gal3 binds carbohydrates to extend IDO's joint residence time. In this study, we evaluated IDO-Gal3's ability to alter OA-associated inflammation and pain-related behaviors in a rat model of established knee OA.

Intra-Articular Delivery of an Indoleamine 2,3-Dioxygenase Galectin-3 Fusion Protein for Osteoarthritis Treatment in Male Lewis Rats.

: Controlling joint inflammation can improve osteoarthritis (OA) symptoms; however, current treatments often fail to provide long-term effects. We have developed an indoleamine 2,3-dioxygenase and galectin-3 fusion protein (IDO-Gal3). IDO converts tryptophan to kynurenines, directing the local environment toward an anti-inflammatory state; Gal3 binds carbohydrates and extends IDO's joint residence time.

Suppression of local inflammation via galectin-anchored indoleamine 2,3-dioxygenase.

The treatment of chronic inflammation with systemically administered anti-inflammatory treatments is associated with moderate-to-severe side effects, and the efficacy of locally administered drugs is short-lived. Here we show that inflammation can be locally suppressed by a fusion protein of the immunosuppressive enzyme indoleamine 2,3-dioxygenase 1 (IDO) and galectin-3 (Gal3). Gal3 anchors IDO to tissue, limiting the diffusion of IDO-Gal3 away from the injection site.

Fast nanoparticle rotational and translational diffusion in synovial fluid and hyaluronic acid solutions.

Nanoparticles are under investigation as diagnostic and therapeutic agents for joint diseases, such as osteoarthritis. However, there is incomplete understanding of nanoparticle diffusion in synovial fluid, the fluid inside the joint, which consists of a mixture of the polyelectrolyte hyaluronic acid, proteins, and other components. Here, we show that rotational and translational diffusion of polymer-coated nanoparticles in quiescent synovial fluid and in hyaluronic acid solutions is well described by the Stokes-Einstein relationship, albeit with an effective medium viscosity that is much smaller than the macroscopic low shear viscosity of the fluid.

The clearance and biodistribution of magnetic composite nanoparticles in healthy and osteoarthritic rat knees.

Intra-articular injections are the most direct route for administering osteoarthritis (OA) therapies, yet how drug carriers distribute within the joint remains understudied. To this end, we developed a magnetic composite nanoparticle that can be tracked with fluorescence in vivo via an in vivo imaging system (IVIS), and quantified ex vivo via electron paramagnetic resonance (EPR) spectroscopy. Using this particle, the effects of age and OA pathogenesis on particle clearance and distribution were evaluated in the medial meniscus transection model of OA (5-, 10-, and 15-month old male Lewis rats).

The effects of age on the severity of joint damage and intra-articular inflammation following a simulated medial meniscus injury in 3, 6, and 9 month old male rats.

: Aging is a known risk factor for osteoarthritis (OA). Several transgenic rodent models have been used to investigate the effects of accelerated or delayed aging in articular joints. However, age-effects on the progression of post-traumatic OA are less frequently evaluated.