Anti-inflammatory supramolecular hydrogel loaded chicoric acid based on graphene oxide modified hyaluronic acid and polyethylene glycol for rheumatoid arthritis treatment.

Chicoric acid (CA) as one of Chinese medicines had anti-inflammatory, less gastrointestinal irritation, less drug-resistance and low cost properties compared with chemical synthesized drug and biologics for rheumatoid arthritis (RA) treatment. To make CA preciously and effectly RA therapy, we firstly developed a supramolecular hydrogel (GHCAP) comprising β-cyclodextrin and graphene oxide (GO) modified hyaluronic acid (CD-HA-GO) as the "host" polymer and adamantane-modified four-arm polyethylene glycol (PEG-AD) as the "guest" polymer, and then the CA was loaded into the supramolecular hydrogel (DGHCAP). The results showed that DGHCAP exhibited injectable, high modulus, high CA loading rate (43.38 %) and slow CA releasing ratio (releasing 80 % in 80 h) compared with those of the supramolecular hydrogel without GO (DHCAP). Moreover, the DGHCAP demonstrated excellent compatibility and effect anti-inflammatory (down regulated proinflammatory cytokines such as IL-1β, IL-6, TNF-α and iNOs) in both in vitro and in vivo assays. The supramolecular hydrogels loaded Chinese medicine could provide another method to treat RA in clinical.