@article{3026976,
    title = "Caveolar uptake and endothelial-protective effects of nanostructured lipid carriers in acid aspiration murine acute lung injury",
    author = "Kardara, M. and Hatziantoniou, S. and Sfika, A. and Vassiliou, A.G. and Mourelatou, E. and Magkou, C. and Armaganidis, A. and Roussos, C. and Orfanos, S.E. and Kotanidou, A. and Maniatis, N.A.",
    journal = "Pharmaceutical Research",
    year = "2013",
    volume = "30",
    number = "7",
    pages = "1836-1847",
    issn = "0724-8741, 1573-904X",
    doi = "10.1007/s11095-013-1027-2",
    keywords = "albumin;  caveolin 1;  coat protein;  curcumin;  hydrochloric acid;  interleukin 6;  interleukin 8;  lipopolysaccharide;  nanoparticle;  nanostructured lipid carrier;  protein p42;  protein p44;  sodium chloride;  thrombin;  unclassified drug, acid aspiration;  actin filament;  acute lung injury;  animal experiment;  animal model;  animal tissue;  article;  caveola;  cell free system;  cell membrane permeability;  controlled study;  cytokine production;  drug efficacy;  drug mechanism;  drug stability;  emulsion;  endosome;  flow cytometry;  fluorescence;  human;  human cell;  inflammatory cell;  male;  microvascular endothelial cell;  mouse;  neutrophil;  nonhuman;  particle size;  physical chemistry;  priority journal;  protein degradation;  protein determination;  protein expression;  scoring system;  signal transduction;  single drug dose, Acute Lung Injury;  Animals;  Blood Coagulation;  Caveolae;  Caveolin 1;  Cell Line;  Cytokines;  Endothelial Cells;  Humans;  Lung;  Male;  Mice;  Mice, Inbred C57BL;  Nanostructures;  Permeability;  Phospholipids;  Thrombin;  Triglycerides",
    abstract = "Purpose: 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. © 2013 Springer Science+Business Media New York."
}