Microneedles containing Cucumaria frondosa polysaccharides and 3-acetylaconitine exert analgesic, anti-inflammatory and chondroprotective activity for knee osteoarthritis

3-Acetylaconitine (AAC) is a commercially analgesic drug for arthritis, however, due to its narrow safety range, its clinical application is limited. The objective of the study was to investigate the combined effect of Cucumaria frondosa polysaccharide (CFP) and AAC in microneedles on knee osteoarthritis (KOA). The characterization of microneedles was conducted and a rat model of monosodium iodoacetate (MIA)-induced KOA was established to evaluate the anti-inflammatory and analgesic activity in this study. The inhibitory effects on cartilage degradation and synovial inflammation were determined by morphological observation of the knee joint, pathological and imaging results. The von Frey pain threshold and hind limb weight bearing test were used to evaluate the effect of microneedles on pain relief. The results showed that microneedles had the mechanical strength to penetrate the skin and dissolved well in the skin for drug delivery within 30 min after patch administration. Furthermore, AAC-MN and CFP-AAC-MN both played roles in relieving pain, reducing cartilage degeneration and inhibiting synovial inflammation in KOA. In summary, CFP combined with AAC loading into microneedles exhibited higher skin penetration and more advantages in inhibiting cartilage damage and inflammation compared to AAC alone.