Development of a novel immunoliposomal delivery system for regulation of inflammation in target organs in murine models of Systemic Lupus Erythematosus

Abstract

Murine models of Systemic Lupus Erythematosus have established the importance of local inflammatory responses and the end organ in the pathogenesis of nephritis. The mesangial cells of the renal glomerulus are key players in this process. However, there are no unique cell surface markers identified for murine and human mesangial cells. Our study shows that α8 is expressed in mouse glomeruli and increases with renal disease making it a potential candidate for immunotargetting of therapeutic agents to the glomerular mesangium. We used a novel strategy of sized liposomes composed of specific lipids conjugated to rabbit anti‐α8 intergrin antibody to target the glomerular mesangium. The anti‐α8 immunoliposomes (α8‐IL) were loaded with a fluorescent dye (DiI) to study trafficking of the immunoliposomes following tail vein injection. DiI was rapidly detected by fluorescence microscopy in glomeruli of mice injected with α8‐IL indicating intracellular uptake. Although expression of α8 intergin has been shown in the lung, brain and interstitial myofibroblasts, the sized liposomal preparation could not access these tissues. A small (<5%) of CD11b+ cells carrying DiI were detected in spleen, liver and lung. Control DiI loaded rabbit IgG ‐IL did not traffic to the glomeruli. This study establishes a novel therapeutic modality for the treatment of glomerular disease and targeted drug therapy in lupus nephritis.