Effect of nanoencapsulation using poly (lactide-co-glycolide) (PLGA) on anti-angiogenic activity of bevacizumab for ocular angiogenesis therapy

Biomed Pharmacother. 2018 Nov:107:1056-1063. doi: 10.1016/j.biopha.2018.08.092. Epub 2018 Aug 25.

Abstract

Antibody-based therapy is an effective strategy for treating ocular angiogenesis. However, short-acting efficacy and poor treatment compliance usually occurs in clinical practices. Thus, it is required to develop a drug delivery system to improve the bioavailability and decrease the toxicity of anti-angiogenic antibody. Bevacizumab is a recombinant humanized monoclonal antibody against vascular endothelial growth factor (VEGF). In this study, bevacizumab was encapsulated into poly (lactide-co-glycolide) (PLGA) nanoparticles. PLGA encapsulation could prolong the residency of bevacizumab in the vitreous and aqueous humor and produce long-lasting drug concentrations. Bevacizumab-encapsulated PLGA had no significant cytotoxicity and tissue toxicity effect in vitro and in vivo. In vitro studies showed that bevacizumab-encapsulated PLGA was more effective than bevacizumab in inhibiting VEGF-mediated endothelial cell proliferation, migration and tube formation. In vivo studies showed that bevacizumab-encapsulated PLGA enhanced the anti-angiogenic efficiency of bevacizumab for treating corneal neovascularization and retinal neovascularization. Thus, bevacizumab-encapsulated PLGA could increase the bioavailability and decrease the toxicity of bevacizumab during ocular angiogenesis therapy.

Keywords: Bevacizumab; Ocular angiogenesis; PLGA; VEGF.

Publication types

  • Comparative Study

MeSH terms

  • Angiogenesis Inhibitors / administration & dosage*
  • Angiogenesis Inhibitors / pharmacology
  • Angiogenesis Inhibitors / toxicity
  • Animals
  • Aqueous Humor / metabolism
  • Bevacizumab / administration & dosage*
  • Bevacizumab / pharmacology
  • Bevacizumab / toxicity
  • Biological Availability
  • Corneal Neovascularization / drug therapy*
  • Corneal Neovascularization / pathology
  • Drug Carriers / chemistry
  • Drug Delivery Systems
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Nanoparticles
  • Particle Size
  • Polylactic Acid-Polyglycolic Acid Copolymer / chemistry
  • Retinal Neovascularization / drug therapy*
  • Retinal Neovascularization / pathology
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors
  • Vitreous Body / metabolism

Substances

  • Angiogenesis Inhibitors
  • Drug Carriers
  • Vascular Endothelial Growth Factor A
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Bevacizumab