Cyclodextrin nanosponges based site-retentive controlled release system for treatment of rheumatic arthritis

Rheumatoid arthritis (RA) is an autoimmune disorder characterized by chronic inflammatory disease of joints. Methotrexate (MTX) is the choice of drug in the treatment of RA due to its prominent immunosuppressant effect and anti-inflammatory effect via an increase in cyclic adenosine monophospate (cAMP) and adenosine-based activity. Our study investigated the local effect of MTX loaded nanosponges in the gel (nanogel) which could be of potential for solubility enhancement, prolonged drug release and retention time, reduced systemic adverse effect, and enhanced anti-arthritic activity. MTX loaded beta-cyclodextrin based nanosponges (MTX-NS) were successfully prepared and characterized by FTIR and NMR. Prepared MTX-NS was evaluated for drug loading, particle size, and morphology. Subsequently, MTX-NS was formulated in a gel-based system, which was evaluated for gelation time, gelation temperature, in-vitro cell line study, and in-vitro drug release. A sustained drug release profile was observed with the developed nanogel. The cell viability of the MTX-NS and nanogel was determined in macrophage cells (RAW264.7) which indicated that nanogel was found to be effective and safe compared to MTX-NS and MTX. The scratch assay indicated that cell migration was significantly inhibited with MTX-NS. Further, the in-vivo study of nanogel was performed using Freund's complete adjuvant-induced inflammation model that confirms the superior anti-arthritic activity of the developed formulation.