Advances in drug delivery systems for Osteoarthritis therapy: exosomes, microparticles, nanoparticles, and hydrogels.

Osteoarthritis is a debilitating chronic joint disorder characterized by cartilage degradation, inflammation, and pain. It significantly impacts the quality of life, particularly in elderly populations. Traditional treatment methods, such as local and systemic drug administration, are limited by poor drug retention, low therapeutic efficacy, and systemic side effects. Recent advancements in drug delivery systems have emerged as promising strategies to overcome these limitations, offering targeted and sustained therapeutic effects, including promoting chondrocyte proliferation and migration, reducing extracellular matrix degradation, and so on. This review highlights the progress in various innovative drug delivery systems, including exosomes, microparticles, nanoparticles, and hydrogels, which have shown promising results in preclinical studies. Exosomes, particularly those derived from mesenchymal stem cells, demonstrate significant potential in promoting cartilage repair, modulating inflammation, and facilitating cell communication. Microparticles composed of natural or synthetic polymers prolong intra-articular drug retention and provide controlled release. Stimuli-responsive nanoparticles, which react to pathological cues like reactive oxygen species, pH, and enzymes, allow precise drug release within the OA microenvironment. Hydrogels offer versatile platforms for sustained delivery and tissue scaffolding, with responsive systems adapting to joint conditions. Despite their promising preclinical results, challenges remain in standardization, manufacturing scalability, and long-term safety. The continued development and clinical translation of these advanced systems hold great potential to revolutionize osteoarthritis therapy by improving efficacy, reducing side effects, and promoting joint tissue regeneration.