Dexamethasone-Loaded Injectable In-situ Thermal Crosslinking Magnetic Responsive Hydrogel for the Physiochemical Stimulation of Acupoint to Suppress Pain in Sciatica Rats

The physicochemical stimulation of acupoints is a widespread treatment strategy for different diseases, such as sciatica. Its efficacy is mainly based on the temporal and spatial modulation of the physicochemical properties of the acupoints. The existing therapies based on the stimulation of acupoints have certain disadvantages. Therefore, in this study, injectable dexamethasone (DXM)- and magnetic Fe 3 O 4 nanoparticles-loaded chitosan/β-glycerophosphate (CS/GP) thermal crosslinking hydrogels were prepared, thereby improving the performance of embedding materials. The sciatica rat models were established to compare the therapeutic effects of hydrogels and catgut. The DXM or Fe 3 O 4 -loaded CS/GP hydrogels were compared in terms of their gelation kinetics, release kinetics, magnetic responsiveness in-vitro, and biocompatibility as well as their analgesic effects on the chronic constriction injury of the sciatic nerve (CCI) rats in-vivo. The CS/GP/Fe 3 O 4 /DXM hydrogel showed comparable gelation kinetics and good magnetic responsiveness in-vitro. This hydrogel could relieve sciatica by reducing the expression levels of inflammatory factors in serum, inhibiting the p38MAPK (p38, mitogen-activated protein kinase) phosphorylation, and decreasing the expression level of the P2X4 receptor (P2X4R) in the spinal dorsal horn. In conclusion, the DXM or Fe 3 O 4 -loaded CS/GP hydrogels can be considered as a treatment option for the physiochemical stimulation therapy of acupoints to improve sciatica.