title: Conjugation of curcumin-loaded lipid nanoemulsions with cell-penetrating peptides increases their cellular uptake and enhances the anti-inflammatory effects in endothelial cells.
abstract: OBJECTIVE
  To prepare and characterize in vitro and in vivo lipid nanoemulsions (LN) loaded with curcumin (Cm) and functionalized with a cell-penetrating peptide.
  
  
  METHODS
  Curcumin-loaded lipid nanoemulsions (CmLN) functionalized with a nona-arginine peptide (R9-CmLN) have been obtained, characterized and optimized for size, entrapment efficiency and in vitro Cm release. The interaction of R9-CmLN with human endothelial cells (HEC) was investigated using cultured EA.hy926 cells, and in vivo biodistribution studies were performed using C57BL6 mice.
  
  
  RESULTS
  When used in therapeutically relevant concentration, R9-CmLN have low haemolytic activity, low cytotoxicity on HEC, and show anti-inflammatory effects by reducing the monocytes adhesion to TNF-α activated HEC. Moreover, HEC uptake and internalization of R9-CmLN was significantly higher compared to the non-functionalized CmLN. In vivo biodistribution studies in mice revealed a higher accumulation of R9-CmLN in the liver and the lungs compared to CmLN and the body clearance of the both nanoformulations after 72 h.
  
  
  CONCLUSIONS
  Cell-penetrating peptides-functionalized CmLN have superior characteristics compared to their non-functionalized counterparts: are more efficiently internalized by the cells, produces anti-inflammatory effects in HEC and when administrated intravenously in mice exhibit increased accumulation in the liver and the lungs, suggesting their potential therapeutic applications in different inflammatory pathologies localized in the liver or the lungs.
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.
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 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.|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: Emanuel
authors.initials: E
authors.lastname: Dragan
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: Ana-Maria
authors.initials: AM
authors.lastname: Gan
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: Alina
authors.initials: A
authors.lastname: Constantin
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.initials: M
authors.lastname: Calin
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D002460:Cell Line; D057846:Cell-Penetrating Peptides / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D003474:Curcumin / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D004337:Drug Carriers / Q000737:chemistry*; D004339:Drug Compounding; D004655:Emulsions; D042783:Endothelial Cells / Q000187:drug effects* / Q000276:immunology; D006801:Humans; D008810:Mice, Inbred C57BL; D049329:Nanostructures / Q000737:chemistry*; D010713:Phosphatidylcholines / Q000737:chemistry*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D057846:Cell-Penetrating Peptides; D004337:Drug Carriers; D004655:Emulsions; D010713:Phosphatidylcholines; D003474:Curcumin
keywords: biodistribution; cell-penetrating peptides; curcumin; endothelial cells; lipid nanoemulsions