TY - JOUR T1 - Site-Specific Inhibition of Glomerulonephritis Progression by Targeted Delivery of Dexamethasone to Glomerular Endothelium JF - Molecular Pharmacology JO - Mol Pharmacol SP - 121 LP - 131 DO - 10.1124/mol.107.034140 VL - 72 IS - 1 AU - Sigridur A. Ásgeirsdóttir AU - Jan A. A. M. Kamps AU - Hester I. Bakker AU - Peter J. Zwiers AU - Peter Heeringa AU - Karen van der Weide AU - Harry van Goor AU - Arjen H. Petersen AU - Henriëtte Morselt AU - Henk E. Moorlag AU - E. Steenbergen AU - Cees G. Kallenberg AU - Grietje Molema Y1 - 2007/07/01 UR - http://molpharm.aspetjournals.org/content/72/1/121.abstract N2 - Glomerulonephritis represents a group of renal diseases with glomerular inflammation as a common pathologic finding. Because of the underlying immunologic character of these disorders, they are frequently treated with glucocorticoids and cytotoxic immunosuppressive agents. Although effective, use of these compounds has limitations as a result of toxicity and systemic side effects. In the current study, we tested the hypothesis that targeted delivery of dexamethasone (dexa) by immunoliposomes to activated glomerular endothelium decreases renal injury but prevents its systemic side effects. E-selectin was chosen as a target molecule based on its disease-specific expression on activated glomerular endothelium in a mouse anti-glomerular basement membrane glomerulonephritis. Site-selective delivery of AbEsel liposome-encapsulated dexamethasone strongly reduced glomerular proinflammatory gene expression without affecting blood glucose levels, a severe side effect of administration of free dexamethasone. Dexa-AbEsel liposomes reduced renal injury as shown by a reduction of blood urea nitrogen levels, decreased glomerular crescent formation, and down-regulation of disease-associated genes. Immunoliposomal drug delivery to glomerular endothelium presents a powerful new strategy for treatment of glomerulonephritis to sustain efficacy and prevent side effects of potent anti-inflammatory drugs. The American Society for Pharmacology and Experimental Therapeutics ER -