Modification of amniotic membrane as a depot carrier for bevacizumab - an in-vitro model for a slow release mechanism

Curr Eye Res. 2013 Apr;38(4):445-50. doi: 10.3109/02713683.2012.757326. Epub 2013 Feb 13.

Abstract

Purpose: 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.

Materials and 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).

Conclusion: 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.

MeSH terms

  • Amnion / metabolism*
  • Amnion / transplantation*
  • Angiogenesis Inhibitors / pharmacology
  • Antibodies, Monoclonal, Humanized / pharmacology*
  • Bevacizumab
  • Cornea / blood supply
  • Cornea / metabolism
  • Corneal Neovascularization / drug therapy*
  • Corneal Neovascularization / prevention & control
  • Corneal Ulcer / drug therapy*
  • Delayed-Action Preparations / pharmacology
  • Drug Carriers*
  • Humans
  • Organ Culture Techniques
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors

Substances

  • Angiogenesis Inhibitors
  • Antibodies, Monoclonal, Humanized
  • Delayed-Action Preparations
  • Drug Carriers
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Bevacizumab