Hyaluronic acid methacrylate microneedles loaded with astaxanthin alleviate rheumatoid arthritis by downregulating the PI3K-AKT pathway

• Our study for the first time revealed that astaxanthin can effectively alleviate rheumatoid arthritis by down-regulating the PI3K-AKT pathway. • 10% hyaluronic methacrylate hydrogel microneedles exhibited excellent skin-penetrating ability, biosafety, and sustained-release properties. • Our findings provided a new strategy for RA treatment and highlighted the clinical translation potential of this approach. Current therapeutic approaches for rheumatoid arthritis (RA) exhibit limitations, including low specificity and numerous adverse effects, thereby necessitating the discovery of effective and patient-friendly treatment modalities. We employed astaxanthin (ATX) for RA treatment due to its unique biological properties. Utilizing integrated bioinformatics analysis methods, we identified that ATX may ameliorate RA by downregulating the PI3K-ATK pathway. This hypothesis was confirmed in vitro through colony formation, wound healing, transwell, and western blot experiments, thereby ensuring the originality of our research. To address the drawbacks of traditional oral treatments, we successfully developed hyaluronic acid methacrylate hydrogel ATX microneedles (HAMA/ATX MNs), which are characterized by excellent skin-penetrating ability, biosafety, and sustained-release properties. By application the HAMA/ATX MNs on adjuvant-induced arthritis (AIA) mice model, induced by injecting complete Freund’s adjuvant into the right hind paw, we validated the efficacy and advantages of HAMA/ATX MNs in alleviating RA-related symptoms in vivo. These findings collectively propose a novel strategy for RA treatment and underscore the clinical translational potential of this approach.