A new LNPs (30-n-LNPs) formulation with increasing phospholipids is investigated as a possible mRNA delivery system for treating Inflammatory Bowel Diseases. Compared to LNPs with benchmark composition (b-LNPs), n-LNPs containing 30% distearoylphosphatidylcholine (DSPC) are well tolerated following intravenous administration and display natural targeting toward the inflamed colon in dextran sodium sulfate (DSS)-colitis bearing mice, while de-targeting clearing organs such as the liver and spleen. Using interleukin-10-encoding mRNA as therapeutic cargo, n-LNPs demonstrated a reduction of pathological burden in colitis-bearing mice. n-LNPs represent a starting point further to investigate the influence of LNPs composition on systemic biodistribution, ultimately opening new therapeutic modalities in different pathologies.
Rampado R. et al (2025) Lipid Nanoparticles With Fine-Tuned Composition Show Enhanced Colon Targeting as a Platform for mRNA Therapeutics. Advanced Science. PDF