Brucine-loaded hydrogel microneedles for sustained anti-inflammatory therapy in rheumatoid arthritis: programmable drug release and detachable design.

This study aimed to develop a brucine (Bru) hydrogel-forming microneedle (Bru-HFM) delivery system that could achieve long-term, programmed drug release, through adjusting degree of cross-linking in polyvinyl alcohol (PVA)/carbomer 934P (CP) hydrogel. A one-way orthogonal experiment and a Franz diffusion cell were employed to optimize the preparation process. The resulting Bru-HFM exhibited favorable appearance, mechanical strength, and swelling properties. The drug release performance of the different drug-carrying sites of HFMs was compared. The results illustrated that in vivo drug release rate over 144 h was significantly higher in the needle body-carrying group (95.32%) than in the whole-microneedle (51.85%) and back-lining groups (57.39%). The amount of residue in the back-lining group was obvious, in line with expectations. The burst release rate of 78.81% could meet the high-dose demand during the acute phase of inflammation, whereas continuous release through the cross-linking network over 48-144 h achieved a total release rate of 95.32%. This covered the maintenance phase of chronic inflammation treatment, and the microneedles remained structurally intact at the end of drug release, permitting their detachable. The general pharmacodynamic evaluation results demonstrated that the pathological state of the ankle joints of rats with collagen-induced arthritis was significantly improved in the needle body-carrying group, which also exhibited significantly reduced serum levels of IL-6, IL-17, and TNF-α (all P < 0.05), indicating a significant therapeutic effect on rheumatoid arthritis. This study provides a new strategy and theoretical basis for designing HFMs for programmed drug release and inflammatory disease treatment.