Cartilage-targeted drug nanocarriers for osteoarthritis therapy

Osteoarthritis (OA) is a joint disease common worldwide. Currently, no disease-modifying osteoarthritis drugs (DMOADs) have successfully passed clinical trials, often due to a lack of cartilage penetration. Thus, targeting the extracellular matrix (ECM) is a major priority. The design of cartilage-targeting drug delivery systems (DDSs) for intra-articular administration requires consideration of the physicochemical properties of articular cartilage, such as its porosity and negative fixed charge. Various positively charged biomaterials such as polyaminoacids, proteins, polymers, and lipids can be used as DDSs to enhance cartilage penetration. Cationic nanocarriers interact electrostatically with anionic glycosaminoglycans of the ECM, ensuring passive cartilage-targeting penetration and prolonged retention. Active targeting strategies involve DDSs surface decoration using antibodies or peptides with a strong affinity for collagen II and chondrocytes in the cartilage. This review presents all the relevant bio-physicochemical properties of healthy and OA cartilages, as well as state-of-the-art intra-articular cartilage-targeted DDSs, intending to better understand the recent advances in the application of cartilage-targeting delivery systems for OA therapy.