The clearance and biodistribution of magnetic composite nanoparticles in healthy and osteoarthritic rat knees

Intra-articular injections are the most direct route for administering osteoarthritis (OA) therapies, yet how drug carriers distribute within the joint remains understudied. To this end, we developed a magnetic composite nanoparticle that can be tracked with fluorescence in vivo via an in vivo imaging system (IVIS), and quantified ex vivo via electron paramagnetic resonance (EPR) spectroscopy. Using this particle, the effects of age and OA pathogenesis on particle clearance and distribution were evaluated in the medial meniscus transection model of OA (5-, 10-, and 15-month old male Lewis rats). At 9 weeks after meniscus transection, composite nanoparticles were injected and joint clearance was assessed via IVIS. At 2 weeks after injection, animals were euthanized and particle distribution was quantified ex vivo via EPR spectroscopy. IVIS and EPR spectroscopy data indicate a predominant amount of particles remained in the joint after 14 days. EPR spectroscopy data suggests particles cleared more slowly from OA knees than from the contralateral control, with particles clearing more slowly from 15-month old rats than from 5- and 10-month old rats. This study demonstrates the importance of including both age and OA as factors when evaluating nanoparticles for infra-articular drug delivery.