Comparison of long-acting bevacizumab formulations in the treatment of choroidal neovascularization in a rat model

J Ocul Pharmacol Ther. 2011 Jun;27(3):219-24. doi: 10.1089/jop.2010.0158. Epub 2011 May 16.

Abstract

Objective: The objective of this study was to compare the reduction in size of experimentally induced choroidal neovascularization (CNV) in rat eyes treated with bevacizumab, poly(ethylene-glycol) (PEG)-bevacizumab conjugate (b-PEG), and poly(lactic-co-glycolic acid) (PLGA)-encapsulated bevacizumab (b-PLGA).

Methods: Forty-eight eyes from 24 rats were divided into 4 groups of 12 eyes. In each group, 3 eyes were assigned to a treatment subgroup, each receiving a different injection-control, bevacizumab, b-PEG, and b-PLGA. In all eyes, laser photocoagulation was used to rupture Bruch's membrane. In group 1, laser was followed by injection, which was then followed by harvesting the rats to assess the CNV area. All 3 steps were separated by a 2-week interval. In groups 2, 3, and 4, injection preceded laser photocoagulation by a variable interval and all rats were harvested 2 weeks postlaser treatment. In group 2, laser and injection were separated by 2 weeks. In group 3, laser followed injection by 4 weeks. In group 4, laser followed injection by 6 weeks. The CNV area was measured for each subgroup and compared against its control. Pairwise comparisons were conducted to assess for statistically significant differences between subgroups.

Results: All subgroups in groups 1, 2, and 4 showed statistically significant reduction of CNV area (P<0.05). In group 3, the b-PEG and b-PLGA subgroups showed a 9.0% (P=0.384) and 20.3% (P=0.077) reduction in CNV area versus control, whereas there was no reduction in CNV area in the bevacizumab subgroup. However, this was not found to be statistically significant. In group 4, b-PEG was more effective than bevacizumab and b-PLGA.

Conclusion: The reduction in CNV area in all treatment subgroups, with the exception of those in group 3, suggests successful creation of the 2 bevacizumab formulations while retaining its active antiangiogenic properties. Further studies varying in dosages and timing of injection and laser are needed to evaluate the formulations' long-acting efficacy.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Angiogenesis Inhibitors / administration & dosage*
  • Angiogenesis Inhibitors / chemistry
  • Angiogenesis Inhibitors / therapeutic use
  • Animals
  • Antibodies, Monoclonal / administration & dosage*
  • Antibodies, Monoclonal / chemistry
  • Antibodies, Monoclonal / therapeutic use
  • Antibodies, Monoclonal, Humanized
  • Bevacizumab
  • Bruch Membrane / radiation effects
  • Choroid / drug effects*
  • Choroid / pathology
  • Choroid / radiation effects
  • Choroidal Neovascularization / drug therapy*
  • Choroidal Neovascularization / pathology
  • Delayed-Action Preparations / administration & dosage
  • Delayed-Action Preparations / chemistry
  • Delayed-Action Preparations / therapeutic use
  • Disease Models, Animal
  • Drug Compounding
  • Fluorescein Angiography / drug effects
  • Fluorescein Angiography / radiation effects
  • Intravitreal Injections
  • Lactic Acid / chemistry
  • Laser Coagulation / adverse effects
  • Male
  • Polyethylene Glycols / chemistry
  • Polyglycolic Acid / chemistry
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Rats
  • Rats, Inbred BN
  • Severity of Illness Index
  • Time Factors
  • Vascular Endothelial Growth Factors / antagonists & inhibitors*

Substances

  • Angiogenesis Inhibitors
  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Delayed-Action Preparations
  • Vascular Endothelial Growth Factors
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polyglycolic Acid
  • Bevacizumab
  • Lactic Acid
  • Polyethylene Glycols