Targeted PLGA Nanoparticle Delivery of Mycophenolate Mofetil: A Novel Approach for Sustained Immunosuppression in Rheumatoid Arthritis

Abstract

Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease that can cause progressive joint damage and disability. Mycophenolate mofetil (MMF), a prodrug of mycophenolic acid, suppresses T- and B-lymphocyte proliferation through inhibition of inosine monophosphate dehydrogenase, but systemic treatment may be limited by gastrointestinal intolerance and other immunosuppression-related adverse effects. This study aimed to develop and evaluate MMF-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles as a potential controlled-release delivery platform. Nanoparticles were prepared using an organic-solvent-based nanoparticle formation method with PLGA as the biodegradable carrier and polyvinyl alcohol (PVA) as stabilizer. A central composite face-centred design was applied to study the influence of polymer and stabilizer concentrations. The formulations were assessed for particle size, polydispersity index, entrapment efficiency, surface morphology, in-vitro drug release, release kinetics and short-term storage stability. Formulation F12 was selected as the optimized formulation. It showed a particle size of 543 nm and a zeta potential of −21.8 mV; reported entrapment efficiencies across the formulation set ranged from 93.3% to 96.5%. Scanning electron microscopy indicated a spherical morphology with smooth surfaces. In-vitro release from F12 reached 92.621% at 480 minutes, with a biphasic profile. The release data fitted zero-order and Korsmeyer–Peppas models closely (R² 0.9864 and 0.9869, respectively). During 90-day storage assessment, particle size and drug content/entrapment measures showed only modest changes. These findings support further investigation of MMF-loaded PLGA nanoparticles; however, targeted delivery to inflamed joints and clinical benefit require direct in-vivo and clinical validation.