title: Caveolar uptake and endothelial-protective effects of nanostructured lipid carriers in acid aspiration murine acute lung injury.
abstract: OBJECTIVE
  Nanostructured lipid carriers (NLC), nanosized phospholipids/triglyceride particles developed for drug delivery, are considered biologically inactive. We assessed the efficacy of unloaded NLC as experimental treatment for acute lung injury (ALI).
  
  
  METHODS
  To induce ALI, C57Black/6 male mice received intratracheal injections of HCl or saline; A single dose of 16 mg/Kg NLC or saline was injected intravenously concomitantly with HCl challenge. NLC uptake mechanisms and effects on endothelial permeability and signaling were studied in cultured endothelial cells and neutrophils.
  
  
  RESULTS
  NLC pre-treatment attenuated pulmonary microvascular protein leak, airspace inflammatory cells, thrombin proteolytic activity and histologic lung injury score 24 h post insult. Using fluorescence measurements and flow cytometry in mouse lung microvascular endothelial cell culture homogenates, we determined that NLC rendered fluorescent by curcumin labeling are taken up by endothelial cells from mice expressing caveolin-1, the coat protein of caveolar endocytic vesicles, but not from caveolin-1 gene-disrupted mice, which lack caveolae. In contrast, conventional emulsions (CE), consisting of larger particles, were not incorporated. In addition, NLC pre-treatment of cultured human lung microvascular endothelial cells abrogated thrombin-induced activation of p44/42, albumin permeability response, actin cytoskeletal remodeling and interleukin-6 production. Finally, NLC but not CE abrogated lipopolysaccharide-triggered interleukin-8 release.
  
  
  CONCLUSIONS
  NLC are engulfed by endothelial caveolae and possess endothelial-protective effects. These novel properties may be of potential utility in ALI.
authors.affiliation: First Department of Critical Care Medicine & Pulmonary Services GP Livanos and M Simou Laboratories, Evangelismos Hospital, Medical School of Athens University, Athens, Greece.
authors.forename: Matina
authors.initials: M
authors.lastname: Kardara
authors.forename: Sophia
authors.initials: S
authors.lastname: Hatziantoniou
authors.forename: Aggeliki
authors.initials: A
authors.lastname: Sfika
authors.forename: Aliki G
authors.initials: AG
authors.lastname: Vassiliou
authors.forename: Elena
authors.initials: E
authors.lastname: Mourelatou
authors.forename: Christina
authors.initials: C
authors.lastname: Muagkou
authors.forename: Apostolos
authors.initials: A
authors.lastname: Armaganidis
authors.forename: Charalambos
authors.initials: C
authors.lastname: Roussos
authors.forename: Stylianos E
authors.initials: SE
authors.lastname: Orfanos
authors.forename: Anastasia
authors.initials: A
authors.lastname: Kotanidou
authors.forename: Nikolaos A
authors.initials: NA
authors.lastname: Maniatis
mesh_terms: D055371:Acute Lung Injury / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D000818:Animals; D001777:Blood Coagulation / Q000187:drug effects; D021941:Caveolae / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051242:Caveolin 1 / Q000378:metabolism; D002460:Cell Line; D016207:Cytokines / Q000032:analysis; D042783:Endothelial Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D049329:Nanostructures / Q000032:analysis / Q000627:therapeutic use*; D010539:Permeability / Q000187:drug effects; D010743:Phospholipids / Q000493:pharmacokinetics / Q000627:therapeutic use*; D013917:Thrombin / Q000378:metabolism; D014280:Triglycerides / Q000493:pharmacokinetics / Q000627:therapeutic use*
chemical_list: D051242:Caveolin 1; D016207:Cytokines; D010743:Phospholipids; D014280:Triglycerides; D013917:Thrombin
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