Development of Spleen Targeting H₂S Donor Loaded Liposome for the Effective Systemic Immunomodulation and Treatment of Inflammatory Bowel Disease

Abstract

Nanoparticles are primarily taken up by immune cells after systemic administration. Thus, they are considered an ideal drug delivery vehicle for immunomodulation. Because the spleen is the largest lymphatic organ and regulates the systemic immune system, there have been studies to develop spleen targeting nanoparticles for immunomodulation of cancer and immunological disorders. Inflammatory bowel disease (IBD) includes disorders involving chronic inflammation in the gastrointestinal tract and is considered incurable despite a variety of treatment options. Hydrogen sulfide (H 2 S) is one of the gasotransmitters that carries out anti-inflammatory functions and has shown promising immunomodulatory effects in various inflammatory diseases including IBD. Herein, we developed a delicately tuned H 2 S donor delivering liposome for spleen targeting (ST-H 2 S lipo) and studied its therapeutic effects in a dextran sulfate sodium (DSS) induced colitis model. We identified the ideal PEG type and ratio of liposome for a high stability, loading efficiency, and spleen targeting effect. In the treatment of the DSS-induced colitis model, we found that ST-H 2 S lipo and conventional long-circulating liposomes loaded with H 2 S donors (LC-H 2 S lipo) reduced the severity of colitis, whereas unloaded H 2 S donors did not. Furthermore, the therapeutic effect of ST-H 2 S lipo was superior to that of LC-H 2 S lipo due to its better systemic immunomodulatory effect than that of LC-H 2 S lipo. Our findings demonstrate that spleen targeting H 2 S lipo may have therapeutic potential for IBD.

Advancements in hydrogel-based drug delivery systems for the treatment of inflammatory bowel disease: a review

“…In contrast, liposomes and nanoparticles may have more limited flexibility. [60][61][62] Therefore, hydrogel-based drug delivery is the preferred choice. However, the choice of hydrogel material depends on several factors, such as the type of drug being delivered, 63 desired release profile, 64 biocompatibility, and the biodegradability of the hydrogel.…”

Size-Dependent In Vivo Transport of Nanoparticles: Implications for Delivery, Targeting, and Clearance

“…Spleen targeted nanoparticles were exploited for modulation of the immune system and immunotherapy. 185,186…”

“…Moreover, nanoparticles with strong affinity to immunocytes (e.g., those adsorb large amounts of immunoglobins in their protein coronas) are more inclined to be retained in the spleen due to the prevalence of immune cells in the spleen. Spleen targeted nanoparticles were exploited for modulation of the immune system and immunotherapy. , …”

Current Status and Future Prospects of Hydrogen Sulfide Donor‐Based Delivery Systems

“…[166] Im et al developed a spleen targeting liposome (ST-H 2 S lipo) loaded with GYY4137 for effective systemic immune regulation and treatment of inflammatory bowel disease. [122] The author speculated that GYY4137 is loaded into the hydrophobic layer of the liposome, and ST-H 2 S lipo showed excellent H 2 S donor loading capacity and stability.…”