title: Ultrasound-enhanced bevacizumab release from echogenic liposomes for inhibition of atheroma progression.
abstract: BACKGROUND
  Bevacizumab (BEV) is a monoclonal antibody to vascular endothelial growth factor (VEGF) that ameliorates atheroma progression by inhibiting neovascularization.
  
  
  OBJECTIVE
  We aimed to determine whether BEV release from echogenic liposomes (BEV-ELIP) could be enhanced by color Doppler ultrasound (US) and whether the released BEV inhibits VEGF expression by endothelial cells in vitro.
  
  
  METHODS
  BEV-ELIP samples were subjected to 6 MHz color Doppler ultrasound (MI = 0.4) for 5 min. We assessed release of BEV with a direct ELISA and with fluoresceinated BEV (FITC-BEV) loaded into ELIP by the same method. Human umbilical vein endothelial cell (HUVEC) cultures were stimulated to express VEGF by 10 nM phorbol-12-myristate 13-acetate (PMA). Cell-associated VEGF levels were determined using a cell-based ELISA.
  
  
  RESULTS
  Overall, US caused an additional 100 µg of BEV to be released or exposed per BEV-ELIP aliquot within 60 min BEV-ELIP treated with US inhibited VEGF expression by 90% relative to non-treated controls and by 70% relative to BEV-ELIP without US. Also, US-treated BEV-ELIP inhibited HUVEC proliferation by 64% relative to untreated controls and by 45% relative to BEV-ELIP without US.
  
  
  CONCLUSIONS
  We have demonstrated that BEV-ELIP retains its VEGF-binding activity in a liposomal formulation and that clinical Doppler US can significantly increase that activity, both by releasing free BEV and by enhancing the surface exposure of the immunoreactive antibody.
authors: a Department of Internal Medicine, Division of Cardiovascular Medicine , University of Texas Health Science Center at Houston , Houston , TX , USA .
authors: Melvin E
authors: ME
authors: Klegerman
authors: a Department of Internal Medicine, Division of Cardiovascular Medicine , University of Texas Health Science Center at Houston , Houston , TX , USA .
authors: Ali K
authors: AK
authors: Naji
authors: b Department of Internal Medicine, Division of Cardiovascular Diseases , University of Cincinnati , Cincinnati , OH , USA , and.|c Biomedical Engineering Program , University of Cincinnati , Cincinnati , OH , USA.
authors: Kevin J
authors: KJ
authors: Haworth
authors: a Department of Internal Medicine, Division of Cardiovascular Medicine , University of Texas Health Science Center at Houston , Houston , TX , USA .
authors: Yuejiao
authors: Y
authors: Zou
authors: a Department of Internal Medicine, Division of Cardiovascular Medicine , University of Texas Health Science Center at Houston , Houston , TX , USA .
authors: Eva
authors: E
authors: Golunski
authors: a Department of Internal Medicine, Division of Cardiovascular Medicine , University of Texas Health Science Center at Houston , Houston , TX , USA .
authors: Tao
authors: T
authors: Peng
authors: a Department of Internal Medicine, Division of Cardiovascular Medicine , University of Texas Health Science Center at Houston , Houston , TX , USA .
authors: George L
authors: GL
authors: Britton
authors: a Department of Internal Medicine, Division of Cardiovascular Medicine , University of Texas Health Science Center at Houston , Houston , TX , USA .
authors: Shao-Ling
authors: SL
authors: Huang
authors: b Department of Internal Medicine, Division of Cardiovascular Diseases , University of Cincinnati , Cincinnati , OH , USA , and.|c Biomedical Engineering Program , University of Cincinnati , Cincinnati , OH , USA.
authors: Christy K
authors: CK
authors: Holland
authors: a Department of Internal Medicine, Division of Cardiovascular Medicine , University of Texas Health Science Center at Houston , Houston , TX , USA .
authors: David D
authors: DD
authors: McPherson
mesh_terms: D000068258:Bevacizumab / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects; D006801:Humans; D008081:Liposomes; D058226:Plaque, Atherosclerotic / Q000188:drug therapy*; D013329:Structure-Activity Relationship; D000069453:Ultrasonic Waves; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000096:biosynthesis
chemical_list: D008081:Liposomes; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab
keywords: Controlled release/delivery; in vitro models; nanotechnology; therapeutic antibodies