Dexamethasone Sodium Phosphate Loaded Modified Cyclodextrin Based Nanoparticles: An Efficient Treatment for Rheumatoid Arthritis

The main aim of the current research was to develop a modified cyclodextrin based nanoparticulate drug delivery system to deliver dexamethasone sodium phosphate (DSP) for the treatment of rheumatoid arthritis (RA). DSP is a glucocorticoid (GC), and its limited application in RA therapy due to poor pharmacokinetics and its severe associated side effects. DSP loaded hydrophobically modified cyclodextrin based nanoparticles (DSP-NPs) prepared by a double emulsion solvent evaporation method. The nanoparticle size was <120 nm, good entrapment efficiency and excellent stability were obtained. TEM study showed that nanoparticles were perfectly spherical shape. The in-vitro drug release from nanoparticle follows the non-Fickian diffusion mechanism. The pharmacokinetic profile of DSP after encapsulation showing the 2.3-fold increase in AUC and extended mean residence time, which increases the chances of nanoparticles to extravasate into the site of inflammation by the EPR effect. The pharmacodynamic studies in the Adjuvant-induced Arthritis (AIA) rat model showing a significant reduction in arthritic score, paw thickness, and inflammatory cytokine level in serum. Adverse effects evaluation studies demonstrate a significant reduction in the associated undesirable effects on body weight, blood glucose level, renal impairment, and hematological abnormalities compared to marketed formulation. These results suggest that DSP-NPs can be used as an efficient therapy for RA. (C) 2020 American Pharmacists Association (R). Published by Elsevier Inc. All rights reserved.