Chemo-photothermal therapeutic effect of chitosan-gelatin hydrogels containing methotrexate and melanin on a collagen-induced arthritis mouse model

Heat stimulation can promote osteoblast differentiation and bone formation. Combining photothermal therapy and chemotherapy is an effective strategy for treating rheumatoid arthritis (RA). Herein, we prepared chitosan/gelatin/β-glycerophosphate-melanin-methotrexate (CMM) hydrogel that could be used to perform simultaneous chemotherapy and photothermal therapy for patients with RA. The CMM solution was successfully converted to a gel state at body temperature. Due to intrinsic photothermal properties of melanin, CMM hydrogel exhibited effective temperature increase both in vitro and in vivo with increasing time of near-infrared (NIR) laser irradiation. After NIR laser irradiation, 50 % of methotrexate was rapidly released from the hydrogel within 3 h. Its release rate showed an instantaneous increase with additional NIR laser irradiation. After CMM hydrogel was injected directly into the paw joint of each collagen-induced arthritis (CIA) mouse followed by irradiation with a NIR laser (808 nm, 0.5 W/cm2, 3 min), swelling and redness at the inflamed area were significantly alleviated at 14 days after treatment. Micro-CT analysis confirmed that treated joints of mice were similar to normal joints. Hence, CMM hydrogel could be used as an attractive RA therapeutic agent for simultaneous chemo-photothermal therapy.