Hydrodynamic Delivery of IL-10 Gene for Local Immunomodulation in Human Crohn's Disease Tissue: A Proof-of-Concept...

Background/Objectives: Interleukin-10 (IL-10) is a potent anti-inflammatory cytokine that is critical for intestinal immune homeostasis. Despite its therapeutic potential, systemic delivery of IL-10 has failed in clinical trials for inflammatory bowel disease (IBD), largely due to its poor localization and short half-life. Methods: We present a proof-of-concept study demonstrating that hydrodynamic delivery of a naked plasmid bearing the human IL-10 gene to ex vivo human colonic segments from Crohn's disease patients results in localized IL-10 expression and modulation of inflammatory mediators. Results: Compared to venous administration, arterial delivery yielded significantly higher IL-10 mRNA and protein levels, as well as decreased IL-6 and TNF-α expression. Furthermore, nanoparticle tracing confirmed efficient tissue penetration via the arterial route. Conclusions: These findings establish arterial hydrodynamic delivery as a feasible, non-viral strategy for targeted gene therapy in IBD.