Targeting\nSynovial Macrophages with Astaxanthin-Loaded\nLiposomes for Antioxidant Treatment of Osteoarthritis

Osteoarthritis (OA) is a chronic joint disease highly\nassociated\nwith an imbalance in the network of inflammatory factors and typically\ncharacterized by oxidative stress and cartilage damage. Moreover,\nthe specificity of the joint structure makes it difficult for drugs\nto achieve good penetration and effective enrichment in the joint\ncavity. Therefore, therapeutic strategies that increase the specific\ntargeting of drugs to inflammatory joint and incorporate antioxidative\nstress effects are important to improve the efficacy of OA. Here,\nwe developed a folic acid-modified liposomal nanoparticle (AST@Lip-FA)\nloaded with the antioxidant astaxanthin (AST) to enhance the water\nsolubility and stability of AST and to target the delivery of AST\nto the site of OA, leading to a significant improvement in therapeutic\nefficacy. In vitro experiments demonstrated that, due to the recognition\nby FA of the receptor folate receptor β on the surface of activated\nmacrophages, the cellular uptake efficiency of AST@Lip-FA was increased.\nMeanwhile, intracellularly overexpressed inflammatory mediators such\nas reactive oxygen species and nitric oxide were efficiently removed\nby AST@Lip-FA. In addition, in the ACLT-induced OA mouse model, AST@Lip-FA\nwas precisely enriched in the inflamed joints and achieved long-term\nretention, fully utilizing the anti-inflammatory, antioxidant, and\ncartilage-protecting effects of AST to effectively alleviate the progression\nof OA. In summary, AST@Lip-FA has an important prospect as a potential\nand effective therapeutic strategy for OA.