Curcumin delivered by ROS-responsive ibuprofen prodrug based on hyaluronic acid effectively suppressed the rheumatoid arthritis

Abstract

Purpose

Rheumatoid arthritis (RA) is an autoimmune disease with systemic inflammatory. Ibuprofen (IBF) and curcumin (CUR) were the commonly therapeutic ingredients for RA treatment and the combination administration possessed the ideal efficacy, however, the low solubility and lack of targeting produced the significant obstacles for the treatment.

Methods

In this study, the IBF prodrug decorated with the CD44 receptors and ROS-sensitive was prepared and encapsulated with the CUR named CUR@HA-TK-IBF were designed, the characterization of CUR@HA-TK-IBF were performed in vitro and the efficacity effect were evaluated using collagen induced arthritis (CIA) model.

Results

The obtained product CUR@HA-TK-IBF exhibited the diameter of 137.3 ± 4.5 nm, and the morphology of the nanoparticles showed the sphericity via the TEM. In vitro release results indicated that the IBF and CUR could slowly release in the normal environment and quickly release at the H₂O₂ environment. Furthermore, the combination of CUR and IBF could significantly decrease the expression of the proinflammatory factors and the concentration of ROS and COX-2 in vitro. The animal experiment indicated that the CUR@HA-TK-IBF could alleviate the foot tumefaction and decrease the expression of proinflammatory factors in the RA model mice.

Conclusion

The CUR@HA-TK-IBF developed the new approach for co-deliver the IBF and CUR, which provided a new therapeutic strategy for the treatment of RA.