Enhanced accumulation of sialyl Lewis X-carboxymethylpullulan conjugate in acute inflammatory lesion

Purpose. E-selectin is a cell adhesion molecule that is specifically expressed in the inflammatory vascular endothelium in response to cytokines such as IL-1 beta and TNF-alpha, and interacts with specific ligands containing sialyl Lewis X (Neu5Ac alpha 2-3Gal beta 1-4(Fuc alpha 1-3)GlcNAc-, SLe(x)). In order to investigate the ability of E-selectin ligands to target the inflammatory site, the tissue distribution of carboxymethylpullulan (CMPul) modified with SLe(x) was studied. Methods. CMPul conjugates with various saccharides containing SLe(x) and monovalent SLe(x) were intravenously administered to mice with ear edema induced by arachidonic acid, and their distributions to the inflamed ear and other tissues were studied. To determine the microdistributions of these compounds, the inflamed ear was subjected to microautoradiography. Results, After intravenous administration AUC(0.24h) Of SLe(x)-CMPul, which binds to E-selectin, in the inflamed ear was about 300-fold and 2.5-fold higher than that of monovalent SLe(x) and CMPul conjugated with other saccharides, which can not serve as ligands for E-selectin. Microautoradiography also revealed SLe(x)-CMPul accumulated at the microvessels in the inflammatory lesions. Conclusions. SLe(x)-CMPul was found to have the potential to target drugs to the inflammatory lesion.