P-Selectin Targeted Dexamethasone-Loaded Lipid Nanoemulsions: A Novel Therapy to Reduce Vascular Inflammation
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 ac...
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| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2016-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2016/1625149 |
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| author | Viorel Simion Cristina Ana Constantinescu Daniela Stan Mariana Deleanu Monica Madalina Tucureanu Elena Butoi Ileana Manduteanu Maya Simionescu Manuela Calin |
| author_facet | Viorel Simion Cristina Ana Constantinescu Daniela Stan Mariana Deleanu Monica Madalina Tucureanu Elena Butoi Ileana Manduteanu Maya Simionescu Manuela Calin |
| author_sort | Viorel Simion |
| collection | DOAJ |
| description | 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 effects in vitro using cultured EC (EA.hy926 cells) and in vivo using 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 functional in vitro and in vivo, reducing selectively the endothelium activation and the consequent monocyte infiltration and diminishing significantly the lungs’ inflammation, in a mouse model of acute inflammation. |
| format | Article |
| id | doaj-art-c97c502f96bf4ffc8712398ceda7d424 |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2016-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-c97c502f96bf4ffc8712398ceda7d4242025-02-03T01:10:43ZengWileyMediators of Inflammation0962-93511466-18612016-01-01201610.1155/2016/16251491625149P-Selectin Targeted Dexamethasone-Loaded Lipid Nanoemulsions: A Novel Therapy to Reduce Vascular InflammationViorel Simion0Cristina Ana Constantinescu1Daniela Stan2Mariana Deleanu3Monica Madalina Tucureanu4Elena Butoi5Ileana Manduteanu6Maya Simionescu7Manuela Calin8Institute of Cellular Biology and Pathology “Nicolae Simionescu” of the Romanian Academy, Bucharest, RomaniaInstitute of Cellular Biology and Pathology “Nicolae Simionescu” of the Romanian Academy, Bucharest, RomaniaInstitute of Cellular Biology and Pathology “Nicolae Simionescu” of the Romanian Academy, Bucharest, RomaniaInstitute of Cellular Biology and Pathology “Nicolae Simionescu” of the Romanian Academy, Bucharest, RomaniaInstitute of Cellular Biology and Pathology “Nicolae Simionescu” of the Romanian Academy, Bucharest, RomaniaInstitute of Cellular Biology and Pathology “Nicolae Simionescu” of the Romanian Academy, Bucharest, RomaniaInstitute of Cellular Biology and Pathology “Nicolae Simionescu” of the Romanian Academy, Bucharest, RomaniaInstitute of Cellular Biology and Pathology “Nicolae Simionescu” of the Romanian Academy, Bucharest, RomaniaInstitute of Cellular Biology and Pathology “Nicolae Simionescu” of the Romanian Academy, Bucharest, RomaniaInflammation 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 effects in vitro using cultured EC (EA.hy926 cells) and in vivo using 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 functional in vitro and in vivo, reducing selectively the endothelium activation and the consequent monocyte infiltration and diminishing significantly the lungs’ inflammation, in a mouse model of acute inflammation.http://dx.doi.org/10.1155/2016/1625149 |
| spellingShingle | Viorel Simion Cristina Ana Constantinescu Daniela Stan Mariana Deleanu Monica Madalina Tucureanu Elena Butoi Ileana Manduteanu Maya Simionescu Manuela Calin P-Selectin Targeted Dexamethasone-Loaded Lipid Nanoemulsions: A Novel Therapy to Reduce Vascular Inflammation Mediators of Inflammation |
| title | P-Selectin Targeted Dexamethasone-Loaded Lipid Nanoemulsions: A Novel Therapy to Reduce Vascular Inflammation |
| title_full | P-Selectin Targeted Dexamethasone-Loaded Lipid Nanoemulsions: A Novel Therapy to Reduce Vascular Inflammation |
| title_fullStr | P-Selectin Targeted Dexamethasone-Loaded Lipid Nanoemulsions: A Novel Therapy to Reduce Vascular Inflammation |
| title_full_unstemmed | P-Selectin Targeted Dexamethasone-Loaded Lipid Nanoemulsions: A Novel Therapy to Reduce Vascular Inflammation |
| title_short | P-Selectin Targeted Dexamethasone-Loaded Lipid Nanoemulsions: A Novel Therapy to Reduce Vascular Inflammation |
| title_sort | p selectin targeted dexamethasone loaded lipid nanoemulsions a novel therapy to reduce vascular inflammation |
| url | http://dx.doi.org/10.1155/2016/1625149 |
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