Pancreas-specific lipid nanoparticle-mediated interleukin-10 mRNA delivery ameliorates acute pancreatitis.

Acute pancreatitis (AP) is one of the leading gastrointestinal conditions requiring hospitalization. Current management relies mainly on supportive care, and no specific pharmacological treatment is available. Interleukin-10 (IL-10) is a well-studied cytokine with potent anti-inflammatory and immunomodulatory effects. Previous studies have demonstrated the beneficial roles of both endogenous and exogenous IL-10 in mitigating pancreatic and systemic injury during AP. However, clinical translation of IL-10 recombinant protein therapy has been limited. Here, we report the development of a sulfonium lipid nanoparticle (sLNP) system for pancreas-specific IL-10 mRNA delivery in AP. Through formulation optimization, we identified DHSEA-based sLNPs with excellent pancreas-specific mRNA delivery efficiency, high specificity, and good biocompatibility. Administration of IL-10 mRNA/DHSEA during the development and progression of cerulein-induced AP significantly reduced pro-inflammatory cytokine expression, serum amylase levels, and pancreatic tissue damage.