Magnetic nanoemulsions loaded with dexamethasone and ascorbic acid demonstrate therapeutic efficacy in rats with collagenaseinduced osteoarthritis

Abstract

Introduction. Osteoarthritis (OA) is a growing global health concern, significantly impacting patients’ quality of life and placing increasing pressure on healthcare systems. Innovative drug delivery approaches may enhance treatment precision and improve therapeutic outcomes. We present a hybrid intra-articular platform that combines magnetic nanoparticles (MNPs) with nano-emulsions (NEs) engineered to deliver dexamethasone (Dex) and ascorbic acid (AA) as a local therapy for OA. Materials and Methods. The NE–MNP formulations were characterized using DLS, TEM, VSM, and FTIR to evaluate their size, morphology, magnetic properties, and stability. Cytocompatibility was assessed in vitro using MTT and LIVE/DEAD assays. Effects on cellular senescence, wound healing, and chondrogenesis were studied in adipose-derived stem cells (ADSCs) through SA-β-galactosidase activity, Western blotting, immunocytochemistry, scratch assays, and chondrogenic markers. Safety and biodistribution were examined in mice after intraperitoneal administration, while therapeutic efficacy was evaluated in a collagenase-induced OA rat model following a single intra-articular injection. Animals were monitored using blood tests, CRP levels, organ histology, MRI, and joint histology for up to five months. Results. The Dex/AA-loaded NE–MNP carriers were nanosized (20–60 nm), stable, and nonaggregating. In vitro, they reduced senescence markers and promoted ADSC chondrogenesis. In mice, systemic administration showed no significant inflammatory or hematologic effects and no organ damage, aside from mild transient activation of liver Kupffer cells. In the rat OA model, a single injection reduced synovial inflammation and improved cartilage thickness over several months compared with controls. Conclusions. Overall, these findings demonstrate the safety and therapeutic potential of Dex- and AAloaded magnetic nano-emulsions for targeted OA treatment. The platform combines magnetic targeting with multi-drug delivery and shows anti-inflammatory and pro-chondrogenic effects. Further studies in larger animal models are needed to support clinical translation.