Development of Inorganic Polyphosphate-Based Nanoparticles for Drug Delivery into Articular Cartilage

Abstract

Osteoarthritis is a degenerative joint disease which affects the entire joint; however, one of its hallmarks is the progressive degeneration of the articular cartilage layer. Patients suffering from osteoarthritis exhibit chronic pain, stiffness, and a decreased range of motion, greatly affecting their quality of life. No drugs have been approved to stop the progression of osteoarthritis and focus solely on the management of symptoms. This is partly due to the challenges in delivering drugs to afflicted joints, and specifically to cartilage due to its lack of vasculature. While intra-articular injection holds promise for the local administration of drugs, small molecules are rapidly cleared from the synovial fluid. As a result, there is a need to develop effective drug delivery strategies to improve residence times in the joint to elicit a sustained therapeutic effect. Previous studies identified polyphosphate as a pro-anabolic molecule, promoting glycosaminoglycan and collagen accumulation in cartilage constructs. Therefore, polyphosphate may be a therapeutic of interest to address the degeneration of articular cartilage in patients suffering from osteoarthritis. In this study, calcium-polyphosphate and strontium-polyphosphate particles were synthesized and characterized as a potential drug carrier into articular cartilage. Physicochemical characterization revealed that the particles exhibit a spherical morphology, have a negative zeta potential, and are nanoscale in size. Biological characterization in chondrocytes confirmed cellular uptake of the particles and demonstrated a size and concentration-dependent cytotoxicity at high concentrations. Furthermore, treatment of chondrocytes with these particles resulted in a reduction in metabolic activity and cell proliferation, confirming biological effects. Preliminary studies using cartilage explants suggest that the particles can penetrate and be retained in cartilage tissue. Therefore, from the results obtained within this study, the polyphosphate-based particles may be a potential drug delivery strategy for delivery into articular cartilage.