Study of Folate-Modified Carboxymethyl Chitosan-Sinomenine-Curcumin Nanopolymer for Targeted Treatment of Rheumatoid Arthritis.

Sinomenine hydrochloride (SH) has been clinically utilized for many years to treat rheumatoid arthritis (RA) in both oral and injectable forms. However, its low bioavailability, poor targeting, high dosage requirements, and side effects, present significant challenges. This study developed folic acid-carboxymethyl chitosan-modified sinomenine-curcumin nanopolymers (named SCNP) for the targeted treatment of RA, to reduce dosage and side effects. The design of SCNP employs folic acid (FA) as a targeting moiety, facilitating specific binding to the folate receptor (FR) on the surface of macrophages and enabling internalization into activated macrophages via endocytosis, thereby achieving targeted delivery to sites of inflammation. In a rat and cell model of RA, SCNP was found to decrease reactive oxygen species (ROS) and pro-inflammatory factors while increasing the anti-inflammatory factor IL-10 through the NF-κB/NLRP3 pathway. These findings indicate that SCNP has the potential to lower drug dosage, enhance therapeutic efficacy, and minimize side effects such as diarrhea and rash, thereby highlighting its promise as an inflammation-targeting nanopolymer.