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

Asgeirdottir, S. A., Kamps, J. A. A. M., Bakker, H. I., Zwiers, P. J., Heeringa, P., van der Weide, K., van Goor, H., Petersen, A. H., Morselt, H., Moorlag, H. E., Steenbergen, E., Kallenberg, C. G. & Molema, G., Jul-2007, In : Molecular Pharmacology. 72, 1, p. 121-131 11 p.

Research output: Contribution to journalArticleAcademicpeer-review

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.

Original languageEnglish
Pages (from-to)121-131
Number of pages11
JournalMolecular Pharmacology
Volume72
Issue number1
Publication statusPublished - Jul-2007

    Keywords

  • E-SELECTIN IMMUNOCONJUGATE, ADHESION MOLECULES, KINASE INHIBITORS, DRUG-DELIVERY, CELLS, EXPRESSION, LIPOSOMES, LEUKOCYTE, ACTIVATION, NEPHRITIS

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