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.
