Site-specific inhibition of glomerulonephritis progression by targeted delivery of dexamethasone to glomerular endothelium

Sigridur A. Asgeirdottir*, Jan A. A. M. Kamps, Hester I. Bakker, Peter J. Zwiers, Peter Heeringa, Karen van der Weide, Harry van Goor, Arjen H. Petersen, Henriette Morselt, Henk E. Moorlag, E. Steenbergen, Cees G. Kallenberg, Grietje Molema

*Bijbehorende auteur voor dit werk

OnderzoeksoutputAcademicpeer review

69 Citaten (Scopus)

Samenvatting

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 Ab(Esel) liposome-encapsulated dexamethasone strongly reduced glomerular proinflammatory gene expression without affecting blood glucose levels, a severe side effect of administration of free dexamethasone. Dexa-Ab(Esel) 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.

Originele taal-2English
Pagina's (van-tot)121-131
Aantal pagina's11
TijdschriftMolecular Pharmacology
Volume72
Nummer van het tijdschrift1
DOI's
StatusPublished - jul-2007

Citeer dit