β-cyclodextrin-based supramolecular micelles of diosgenin conjugated with anti-CD64 antibody for rheumatoid arthritis

Abstract

Supramolecular polymeric micelles from β-CD offer superior targeted-nano-delivery for efficacious therapy with optimal size, shape, encapsulation efficiency with evasion of RES, enzymatic degradation and high blood circulation time. Rheumatoid arthritis is an autoimmune disease characterized by inflammation of the synovium joint causing restriction in the movement of the joint along with swelling, pain, progressively leading to disability, and early death. This encompasses the fabrication of supramolecular polymeric micelles loaded with diosgenin and conjugated to anti-CD64 antibody for targeted action to the inflamed synovium in arthritis. The diosgenin-loaded supramolecular micelles exhibited particle size of 318.7±27.36 nm, good micellar stability with a zeta potential of -13.1±6.94 mV and encapsulation efficiency of 92.45% with controlled release of 86.58±1.51% drug for 24 h. The anti-arthritic activity was confirmed via pharmacodynamic study using Wistar rats, wherein significant reduction in paw diameter following 14-day treatment was observed from 6.47 mm to 4.59 mm. Furthermore, interleukin IL-15(6.88 pg/mL) and tumor necrosis factor-α (10.81 pg/mL) levels in rat serum were analyzed using ELISA and found to be near the normal range. Thus, DSMs propose to be superior effective alternative treatment carrier for arthritis management with high specificity, upregulation of COX-2, downregulation of ILs, NO, TNF- α and various inflammatory markers.