Amelioration of osteoarthritis through salicylic acid nano-formulated self-therapeutic prodrug for the prolonged launch of salicylic acid to damaged cartilage

As the most prevalent disease globally and with a lack of efficient therapeutic drugs, there is a need for novel strategies to treat osteoarthritis (OA). One approach being explored is the usage of biodegradable polymers as drug-delivery systems for OA treatment. However, a limitation of these polymeric drug carriers is that they do not possess therapeutic efficacy themselves. To address this issue, a new strategy has been developed using an aspirin-like oligomer called poly (salicylic acid) (PSA). The oligomer is synthesized through the self-esterification of salicylic acid (SA), which is a non-steroidal anti-inflammatory drug (NSAID) commonly used to relieve pain and inflammation associated with OA. Self-assembled PSA nanoparticles (PSA NPs) possess a distinctive capability to dynamically modulate the release rate of SA through the manipulation of their morphology. Crucially, SA, as the degradation product of the PSA NPs, has been substantiated to possess a demonstrated capability for capturing reactive oxygen species (ROS). In vitro studies have demonstrated the negligible toxicity of PSA NPs against SW1353 cells. Moreover, in vivo results have indicated that intra-articular injection of PSA NPs resulted in prolonged joint retention and significant alleviation of OA lesions in mice. Both in vitro and in vivo investigations have proved the capacity of PSA NPs to attenuate inflammation and restore the balance of cartilage extracellular matrix (ECM) metabolism through the inhibition of COX-2 and NF-κB p65 expressions. These compelling results suggest that the PSA NPs hold promising potential as an effective therapeutic strategy for OA.