title: P-Selectin Targeted Dexamethasone-Loaded Lipid Nanoemulsions: A Novel Therapy to Reduce Vascular Inflammation.
abstract: Inflammation is a common process associated with numerous vascular pathologies. We hypothesized that targeting the inflamed endothelium by coupling a peptide with high affinity for P-selectin to the surface of dexamethasone-loaded lipid nanoemulsions will highly increase their specific binding to activated endothelial cells (EC) and reduce the cell activation. We developed and characterized dexamethasone-loaded lipid nanoemulsions directed towards P-selectin (PLN-Dex) and monitored their anti-inflammatory effectsin vitrousing cultured EC (EA.hy926 cells) andin vivousing a mouse model of acute inflammation [lipopolysaccharides (LPS) intravenously administered in C57BL/6 mice]. We found that PLN-Dex bound specifically to the surface of activated EC are efficiently internalized by EC and reduced the expression of proinflammatory genes, thus preventing the monocyte adhesion and transmigration to/through activated EC. Given intravenously in mice with acute inflammation, PLN-Dex accumulated at a significant high level in the lungs (compared to nontargeted nanoemulsions) and significantly reduced mRNA expression level of key proinflammatory cytokines such as IL-1β, IL-6, and MCP-1. In conclusion, the newly developed nanoformulation, PLN-Dex, is functionalin vitroandin vivo, reducing selectively the endothelium activation and the consequent monocyte infiltration and diminishing significantly the lungs' inflammation, in a mouse model of acute inflammation.
authors.affiliation: Institute of Cellular Biology and Pathology "Nicolae Simionescu" of the Romanian Academy, Bucharest, Romania.
authors.forename: Viorel
authors.initials: V
authors.lastname: Simion
authors.affiliation: Institute of Cellular Biology and Pathology "Nicolae Simionescu" of the Romanian Academy, Bucharest, Romania; Faculty of Veterinary Medicine, University of Agronomic Sciences and Veterinary Medicine, Bucharest, Romania.
authors.forename: Cristina Ana
authors.initials: CA
authors.lastname: Constantinescu
authors.affiliation: Institute of Cellular Biology and Pathology "Nicolae Simionescu" of the Romanian Academy, Bucharest, Romania.
authors.forename: Daniela
authors.initials: D
authors.lastname: Stan
authors.affiliation: Institute of Cellular Biology and Pathology "Nicolae Simionescu" of the Romanian Academy, Bucharest, Romania; Faculty of Biotechnologies, University of Agronomic Sciences and Veterinary Medicine, Bucharest, Romania.
authors.forename: Mariana
authors.initials: M
authors.lastname: Deleanu
authors.affiliation: Institute of Cellular Biology and Pathology "Nicolae Simionescu" of the Romanian Academy, Bucharest, Romania.
authors.forename: Monica Madalina
authors.initials: MM
authors.lastname: Tucureanu
authors.affiliation: Institute of Cellular Biology and Pathology "Nicolae Simionescu" of the Romanian Academy, Bucharest, Romania.
authors.forename: Elena
authors.initials: E
authors.lastname: Butoi
authors.affiliation: Institute of Cellular Biology and Pathology "Nicolae Simionescu" of the Romanian Academy, Bucharest, Romania.
authors.forename: Ileana
authors.initials: I
authors.lastname: Manduteanu
authors.affiliation: Institute of Cellular Biology and Pathology "Nicolae Simionescu" of the Romanian Academy, Bucharest, Romania.
authors.forename: Maya
authors.initials: M
authors.lastname: Simionescu
authors.affiliation: Institute of Cellular Biology and Pathology "Nicolae Simionescu" of the Romanian Academy, Bucharest, Romania.
authors.forename: Manuela
authors.identifier: 0000-0002-5245-160X
authors.initials: M
authors.lastname: Calin
mesh_terms: D000818:Animals; D018932:Chemokine CCL2 / Q000378:metabolism; D003907:Dexamethasone / Q000737:chemistry*; D004655:Emulsions / Q000008:administration & dosage / Q000737:chemistry*; D005434:Flow Cytometry; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy*; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D049329:Nanostructures / Q000008:administration & dosage / Q000737:chemistry*; D019007:P-Selectin / Q000737:chemistry / Q000627:therapeutic use*
chemical_list: D018932:Chemokine CCL2; D004655:Emulsions; D053583:Interleukin-1beta; D015850:Interleukin-6; D008070:Lipopolysaccharides; D019007:P-Selectin; D003907:Dexamethasone