Diacerein-loaded surface modified iron oxide microparticles (SMIOMPs): an emerging magnetic system for management of osteoarthritis via intra-articular injection.

Abstract

Introduction: Osteoarthritis (OA) is regarded as one of the most prevealent irreversible joint degenerative disorder worldwide. Recently, considerable interest in utilizing intra-articular (IA) injections for managing OA has been raised.

Methods: In this study, IA injectable surface modified iron oxide microparticles (SMIOMPs) loaded with Diacerein (DCN) were developed. The effects of formulation parameters on particle size, entrapment efficiency, and zeta potential were explored using factorial design. The optimized formulation was characterized regarding morphology and in vitro release. Differential scanning calorimetry (DSC) and Fourier-transform infrared spectroscopy (FTIR) were done to assess interactions. Further, sterilization and in vivo performance in rats with induced arthritis has been performed for the optimized formulation.

Results and discussion: The selected optimized system included 2M FeCL3 and 1% chitosan as a surface modifier achieved high drug entrapment of 85.25% with a PS of 1.54 µm and sustained DCN release. Morphological examination of the optimized formulation revealed spherical particles with chitosan coat. DSC and FTIR results indicated the absence of undesired interactions between DCN and the used components. No significant change in the measured parameters was observed following sterilization using gamma radiation. In vivo assessment revealed superior performance for the optimized formulation in reducing cartilage inflammation and degradation. Plasma levels of tumor necrosis factor α and Interleukin-1 beta, as well as knee diameter, were significantly reduced in the treated groups compared to the untreated ones.

Conclusion: Overall, the results suggest that the proposed DCN-loaded SMIOMPs represent a promising advancement in the arena of cartilage regeneration.