Transvascular accumulation of Sialyl Lewis X conjugated liposome in inflamed joints of collagen antibody-induced arthritic (CAIA) mice

Abstract

The aim of the current study was to investigate the specific accumulation of the Sialyl Lewis X (SLX) liposome in inflammation in the collagen-antibody induced arthritic (CAIA) model mice. The SLX-liposome encapsulating fluorescent substance (Cy5.5 or Cy3) was prepared for this study. The SLX-liposome was administered intravenously via the mouse caudal vein. After 1 to 24 h, the accumulation of SLX-liposome was observed using in vivo fluorescent imaging equipment (eXplore Optix), or the knee joints were removed for histological analysis. The in vivo fluorescent imaging showed that the signal was confined to the inflammatory site in the CAIA mice in an inflammatory dependent manner. The signal intensity was stronger at 24 h than at 1 h after injection. In the histological sections, the fluorescent signals were detected in the periarticular soft-tissue, especially in the hyperplastic synovium, including a pannus invasion with inflammatory cells in the CAIA. Intense signals were observed in vessel-like structures 1 h after injection; these were co-labeled with the vascular endothelial cell marker (CD31) and E-selectin, a ligand of the SLX-liposome expressed on activated endothelial cells. The diffused signals from the vessels increased time-dependently at 6 to 24 h after injection. This is the first report to examine the exact localization of the SLXliposome by encapsulated fluorescence in hyperplastic synovial tissue of CAIA mice. These results suggest the feasibility and potential use of SLX-liposome as a vehicle for the active targeting of drug delivery to inflammatory tissue.