Development of Spleen\nTargeting H<sub>2</sub>S Donor\nLoaded Liposome for the Effective Systemic Immunomodulation and Treatment\nof Inflammatory Bowel Disease

Nanoparticles are primarily taken up by immune cells\nafter systemic\nadministration. Thus, they are considered an ideal drug delivery vehicle\nfor immunomodulation. Because the spleen is the largest lymphatic\norgan and regulates the systemic immune system, there have been studies\nto develop spleen targeting nanoparticles for immunomodulation of\ncancer and immunological disorders. Inflammatory bowel disease (IBD)\nincludes disorders involving chronic inflammation in the gastrointestinal\ntract and is considered incurable despite a variety of treatment options.\nHydrogen sulfide (H₂S) is one of the gasotransmitters that\ncarries out anti-inflammatory functions and has shown promising immunomodulatory\neffects in various inflammatory diseases including IBD. Herein, we\ndeveloped a delicately tuned H₂S donor delivering liposome\nfor spleen targeting (ST-H₂S lipo) and studied its therapeutic\neffects in a dextran sulfate sodium (DSS) induced colitis model. We\nidentified the ideal PEG type and ratio of liposome for a high stability,\nloading efficiency, and spleen targeting effect. In the treatment\nof the DSS-induced colitis model, we found that ST-H₂S\nlipo and conventional long-circulating liposomes loaded with H₂S donors (LC-H₂S lipo) reduced the severity of\ncolitis, whereas unloaded H₂S donors did not. Furthermore,\nthe therapeutic effect of ST-H₂S lipo was superior to that\nof LC-H₂S lipo due to its better systemic immunomodulatory\neffect than that of LC-H₂S lipo. Our findings demonstrate\nthat spleen targeting H₂S lipo may have therapeutic potential\nfor IBD.