Intra-articular injection of PLGA/polydopamine core-shell nanoparticle attenuates osteoarthritis progression

Abstract

Osteoarthritis (OA) is a common joint disease characterized by progressive cartilage degeneration, which is regulated by oxidative stress, and there is currently no clinical drug to alleviate its development. Kartogenin (KGN) was found to treat cartilage damage in early OA, but its application is limited by the rapid clearance from synovial fluid. This study synthesized a KGN-loaded nanocarrier based on PLGA/polydopamine core/shell structure to treat OA. The prepared KGN@PLGA/PDA-PEG-E7 nanoparticles could stay in the joint cavity for more than four weeks, ensuring the long-term sustained release of KGN after a single intra-articular injection. Moreover, the polyphenolic structure of PDA makes it effective in scavenging reactive oxygen species (ROS), so the KGN@PLGA/PDA-PEG-E7 NPs could promote chondrogenic differentiation even under oxidative stress conditions. In addition, the BMSCs-targeting peptide E7(EPLQLKM) conferred effective BMSCs affinity to KGN@PLGA/PDA-PEG-E7 NPs, which enhanced the efficacy of inducing cartilage in vitro and in vivo. As a result, the KGN@PLGA/PDA-PEG-E7 nanoparticles could effectively protect cartilage and subchondral bone in a rat ACLT model. In summary, KGN@PLGA/PDA-PEG-E7 nanoparticles can be used for intra-articular injection to effectively alleviate OA progression. This therapeutic strategy can also be extended to the delivery of other drugs or targeting other tissues to treat joint diseases.