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Targeted delivery of celastrol to mesangial cells is effective against mesangioproliferative glomerulonephritis
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Targeted delivery of celastrol to mesangial cells is effective against mesangioproliferative glomerulonephritis
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Journal Article
Targeted delivery of celastrol to mesangial cells is effective against mesangioproliferative glomerulonephritis
2017
Overview
Mesangial cells-mediated glomerulonephritis is a frequent cause of end-stage renal disease. Here, we show that celastrol is effective in treating both reversible and irreversible mesangioproliferative glomerulonephritis in rat models, but find that its off-target distributions cause severe systemic toxicity. We thus target celastrol to mesangial cells using albumin nanoparticles. Celastrol-albumin nanoparticles crosses fenestrated endothelium and accumulates in mesangial cells, alleviating proteinuria, inflammation, glomerular hypercellularity, and excessive extracellular matrix deposition in rat anti-Thy1.1 nephritis models. Celastrol-albumin nanoparticles presents lower drug accumulation than free celastrol in off-target organs and tissues, thereby minimizing celastrol-related systemic toxicity. Celastrol-albumin nanoparticles thus represents a promising treatment option for mesangioproliferative glomerulonephritis and similar glomerular diseases.
Mesangial cell-mediated glomerulonephritis is a frequent cause of kidney disease. Here the authors show that celastrol loaded in albumin nanoparticles efficiently targets mesangial cells, and is effective in rat models.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ Albumin
/ Animals
/ Anti-Inflammatory Agents - administration & dosage
/ Anti-Inflammatory Agents - pharmacology
/ Anti-Inflammatory Agents - therapeutic use
/ Glomerular Mesangium - pathology
/ Glomerulonephritis - drug therapy
/ Glomerulonephritis - pathology
/ Humanities and Social Sciences
/ Mesangial Cells - drug effects
/ Nanoparticles - therapeutic use
/ Organs
/ Rats
/ Rodents
/ Science
/ Toxicity
