Overcoming barriers for intra-articular delivery of disease-modifying osteoarthritis drugs

Despite four decades of research in intra-articular drug delivery systems (DDS) and two decades of advances in disease-modifying osteoarthritis drugs (DMOADs), there is still no clinically available disease-modifying therapy for osteoarthritis (OA). Multiple barriers compromise intra-articular DMOAD delivery. Although multiple exciting approaches have been developed to overcome these barriers, there are still outstanding questions. We make several recommendations that can help in fully overcoming these barriers. Considering OA heterogeneity, we also propose a patient-centered, bottom-up workflow to guide preclinical development of DDS-based intra-articular DMOAD therapies. Overall, we expect this review to inspire paradigm-shifting innovations for developing next-generation DDS that can enable clinical translation of intra-articular DMOADs.