Impact of administration route on nanocarrier biodistribution in a murine colitis model

Abstract

The incidence of inflammatory bowel disease (IBD) is increasing worldwide. Although current diagnostic and disease monitoring tests for IBD sensitively detect gut inflammation, they lack the molecular and cellular specificity of positron emission tomography (PET). In this proof-of-concept study, we use a radiolabeled macrophage-targeted nanocarrier probe ( 64 Cu-NOTA-D500) administered by oral, enema, and intraperitoneal routes to evaluate the delivery route dependence of biodistribution across healthy and diseased tissues in a murine model of dextran sodium sulfate (DSS)-induced colitis. High inter-subject variability of probe uptake in intestinal tissue was reduced by normalization to uptake in liver or total intestines. Differences in normalized uptake between healthy and DSS colitis animal intestines were highest for oral and IP routes. Differences in absolute liver uptake reflected a possible secondary diagnostic metric of IBD pathology. These results should inform the preclinical development of inflammation-targeted contrast agents for IBD and related gut disorders to improve diagnostic accuracy.

Gut‐liver axis: Potential mechanisms of action of food‐derived extracellular vesicles

“…Oral administration can also provide a gradual release of the substance into the bloodstream, contributing to stable and prolonged therapeutic effects. For gut and gut‐related diseases, the oral administration route is particularly effective since it enables direct contact between the drug and the diseased sites (Applegate et al., 2022 ). Compared to other nanoparticles, FEVs are particularly suitable for oral administration due to the following reasons: (1) FEVs are derived from natural sources and have better safety and biocompatibility than synthesized vehicles; (2) Compared to cell‐derived EVs, FEVs resist the harsh conditions in the GI tract and (3) FEVs can crosstalk with gut microbiota, thus directly acting on the gut barrier or indirectly on the remote organs via bacterial metabolites.…”