Phaseolus lunatusL. polysaccharide microneedles loaded with sinomenine hydrochloride for synergistic rheumatoid arthritis management and analgesia.

Rheumatoid arthritis (RA) is a chronic autoimmune disease. In the clinical treatment of RA, the anti-rheumatoid drug sinomenine hydrochloride (SIN) was administered as tablets or injections. It has low oral bioavailability, dose-dependent adverse reactions, poor patient compliance with injections, and fails to resolve patients' early pain problems. We developed a bilayer polyvinylpyrrolidone (PVP)/Phaseolus lunatusL. polysaccharide (PLP) microneedle (MN) to deliver SIN to inflammatory joints. The PVP layer rapidly dissolved and released SIN within 5 min of SIN@PLP MNs penetrating the skin; the PLP layer embedded in the skin functioned as a polymer carrier, releasing SIN continuously for up to 12 h; and 15 % PLP acted as a viscous backing to improve the efficacy of transdermal drug delivery. SIN@PLP MNs effectively inhibited the proliferation of fibroblast-like synoviocytes by scavenging reactive oxygen species (ROS), inhibiting the NF-κB and MAPK pathways, facilitating the polarization of macrophage phenotypes from M1 to M2, and reducing inflammatory cytokines. In an AIA rat model, SIN@PLP MNs reduced cartilage erosion and inflammatory pain. This natural multifunctional microneedle delivery system, which achieves immediate analgesia and sustained synergistic anti-inflammation, provides a novel approach to the safe and effective treatment of RA.