Inhibition of proinflammatory genes in anti-GBM glomerulonephritis by targeted dexamethasone-loaded AbEsel liposomes

摘要

Today many new potent anti-inflammatory drugs do not make it through clinical trials because of severe side effects (23). For these highly active drugs, a targeted delivery approach represents a significant added value for future clinical applicability. Liposomes are high-capacity drug carriers that, when modified with monoclonal antibodies, can be targeted to a target epitope of choice (17). For treatment of glomerulonephritis, glomerular endothelial cells are attractive targets for cell-specific drug delivery. Not only are they in direct contact with the bloodstream and hence well accessible for systemi-cally administered therapeutics, but they also play a pivotal role in the pathological process associated with glomerulonephritis. Because E-selectin is uniquely restricted to activated endothelial cells (26) and is an internalizing receptor, it represents a suitable target for intracellular delivery of drugs that need to exert their pharmacological activity inside endothelial cells (10).