Abstract Summary/Description
Chronic inflammation in inflammatory bowel disease (IBD) contributes to tumorigenesis, underscoring the need for targeted delivery systems capable of administering precise, low doses of therapeutics directly to inflamed colonic regions. Inspired by the colon-targeting properties of ginger-derived nanoparticles (GDNPs), we reversely engineered a novel lipid nanoparticle (nLNP) incorporating the three key lipids identified in GDNPs—phosphatidic acid (PA), monogalactosyldiacylglycerol (MGDG), and digalactosyldiacylglycerol (DGDG). Characterization by dynamic light scattering revealed an average nLNP diameter of 190.4 nm with a zeta potential of -22.3 mV. Orally delivered nLNP showed no significant impact on gut microbiota composition and was confirmed as a safe carrier through in vitro and in vivo toxicity tests. Biodistribution studies demonstrated its potential for oral drug delivery, achieving targeted release in colon tissue. Furthermore, fluorescence-activated cell sorting (FACS) revealed that nLNP is internalized by epithelial cells and macrophages, with uptake significantly enhanced in inflamed colon tissues compared to healthy controls. These findings support the development of the nLNP as a safe and effective inflammation-responsive delivery platform for therapeutic interventions in ulcerative colitis.