Harnessing a Safe Novel Lipid Nanoparticle: Targeted Oral Delivery to Colonic Epithelial and Macrophage Cells in a Colitis Mouse Model.

A novel lipid nanoparticle (nLNP), formulated with three essential lipids to mimic ginger-derived exosomal particles, shows strong potential for delivering IL-22 mRNA specifically to the colon, presenting a unique oral drug delivery system for inflammatory bowel disease (IBD). However, its cellular targets and uptake behavior in healthy versus diseased colons remain unclear. Understanding these aspects is crucial for fully elucidating its targeting effectiveness in inflamed colon tissue. This study investigates the nLNP's cellular targets in healthy and diseased mouse colons. Flow cytometry compared nLNP uptake in healthy mice and a DSS-induced acute colitis model. The results revealed efficient internalization of nLNP by colonic epithelial cells in healthy and inflamed mice. In non-inflamed mice, the small number of colonic macrophages resulted in minimal uptake of nLNP by these cells. In inflamed mice, macrophages migrated to the damaged epithelium, where nLNP uptake was significantly increased, highlighting the nLNP's ability to target both epithelial and macrophage cells during inflammation. Additionally, safety assessments showed that the nLNP neither altered in vitro kinase activities nor exhibited immunotoxicity or induced in vivo toxicity at the maximum tolerated oral dose. These findings underscore the nLNP's safety and potential as a promising epithelial/macrophage-targeted drug delivery platform for oral ulcerative colitis (UC) treatment.