Catherine C Applegate, Hongping Deng, Brittany L Kleszynski, Tzu-Wen L Cross, Christian J Konopka, L Wawrzyniec Dobrucki, Erik R Nelson, Matthew A Wallig, Andrew M Smith, Kelly S Swanson
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Impact of administration route on nanocarrier biodistribution in a murine colitis model.
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 (64Cu-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.
期刊介绍:
Journal of Experimental Nanoscience, an international and multidisciplinary journal, provides a showcase for advances in the experimental sciences underlying nanotechnology and nanomaterials.
The journal exists to bring together the most significant papers making original contributions to nanoscience in a range of fields including biology and biochemistry, physics, chemistry, chemical, electrical and mechanical engineering, materials, pharmaceuticals and medicine. The aim is to provide a forum in which cross fertilization between application areas, methodologies, disciplines, as well as academic and industrial researchers can take place and new developments can be encouraged.