title: Modification of amniotic membrane as a depot carrier for bevacizumab - an in-vitro model for a slow release mechanism.
abstract: OBJECTIVE
  Corneal ulceration may be treated with human amniotic membrane (HAM) while neovascularization remains a common complication of corneal ulceration. As several factors contained within HAM may contribute to reduced corneal scarring, we investigated if HAM may be additionally loaded with bevacizumab and potentially serve as a carrier for anti-vascular endothelial growth factor (VEGF) drugs to provide constant VEGF blockade.
  
  
  METHODS
  Cryo-preserved HAM were incubated with different bevacizumab concentrations in organ culture medium for 2-5 d. Controls were incubated without bevacizumab. Then, all samples were placed into an organ culture medium without bevacizumab for 48 h, 72 h or for 5 d at 37 °C with the medium being changed at all time points. After that, VEGF165 was added to the supernatants for 24 h and free VEGF 165 was measured by ELISA.
  
  
  RESULTS
  Free VEGF was significantly blocked at 48 and 72 h (p < 0.01). VEGF blockade was less pronounced after 1 week. However, as compared to control, VEGF was significantly blocked at all times (p < 0.05).
  
  
  CONCLUSIONS
  In this in-vitro setting, we could demonstrate effective VEGF-blockade for up to 1 week by incubating HAM with bevacizumab. HAMs might be potentially used as a carrier for drugs delivered to the cornea.
authors: Department of Ophthalmology, Ludwig-Maximilians-University, Munich, München, Germany. wolfgang.j.mayer@med.uni-muenchen.de
authors: Wolfgang J
authors: WJ
authors: Mayer
authors: Martin
authors: M
authors: Grüterich
authors: Daniel
authors: D
authors: Kook
authors: Winfried
authors: W
authors: Sigg
authors: Marcus
authors: M
authors: Kernt
authors: Elisabeth M
authors: EM
authors: Messmer
authors: Christos
authors: C
authors: Haritoglou
authors: Anselm
authors: A
authors: Kampik
authors: Armin
authors: A
authors: Wolf
mesh_terms: D000650:Amnion / Q000378:metabolism* / Q000637:transplantation*; D020533:Angiogenesis Inhibitors / Q000494:pharmacology; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology*; D000068258:Bevacizumab; D003315:Cornea / Q000098:blood supply / Q000378:metabolism; D016510:Corneal Neovascularization / Q000188:drug therapy* / Q000517:prevention & control; D003320:Corneal Ulcer / Q000188:drug therapy*; D003692:Delayed-Action Preparations / Q000494:pharmacology; D004337:Drug Carriers; D006801:Humans; D009924:Organ Culture Techniques; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D003692:Delayed-Action Preparations; D004337:Drug Carriers; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab