Identification of TAK-756, A Potent TAK1 Inhibitor for the Treatment of Osteoarthritis through Intra-Articular Administration.

Osteoarthritis (OA) is a chronic and degenerative joint disease affecting more than 500 million patients worldwide with no disease-modifying treatment approved to date. Several publications report on the transforming growth factor β-activated kinase 1 (TAK1) as a potential molecular target for OA, with complementary anti-catabolic and anti-inflammatory effects. We report herein on the development of TAK1 inhibitors with physicochemical properties suitable for intra-articular injection, with the aim to achieve high drug concentration at the affected joint, while avoiding severe toxicity associated with systemic inhibition.

Surface modified cationic PLGA microparticles as long-acting injectable carriers for intra-articular small molecule drug delivery.

Controlled local delivery of therapeutics (small molecule drug crystals or biologics) for knee-associated diseases such as osteoarthritis necessitates patient compliance, ensuring that the injected depot does not trigger local tissue inflammation and immune responses. A local drug delivery strategy that releases drug at a controlled rate while ensuring minimal tolerability issues at the injection site would be an appealing paradigm in intra-articular (IA) therapies. Herein, we report the formulation development and characterization of surface modified PLGA microparticles (MPs) through the surface integration of a cationic lipid, DOTAP (1,2-Dioleoyl-3-trimethylammonium propane).