RT Journal Article
SR Electronic
T1 Site-Specific Inhibition of Glomerulonephritis Progression by Targeted Delivery of Dexamethasone to Glomerular Endothelium
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 121
OP 131
DO 10.1124/mol.107.034140
VO 72
IS 1
A1 Sigridur A. Ásgeirsdóttir
A1 Jan A. A. M. Kamps
A1 Hester I. Bakker
A1 Peter J. Zwiers
A1 Peter Heeringa
A1 Karen van der Weide
A1 Harry van Goor
A1 Arjen H. Petersen
A1 Henriëtte Morselt
A1 Henk E. Moorlag
A1 E. Steenbergen
A1 Cees G. Kallenberg
A1 Grietje Molema
YR 2007
UL http://molpharm.aspetjournals.org/content/72/1/121.abstract
AB 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