Bevacizumab-Conjugated Quantum Dots: In Vitro Antiangiogenic Potential and Biosafety in Rat Retina

J Ocul Pharmacol Ther. 2020 Jul/Aug;36(6):467-483. doi: 10.1089/jop.2019.0108. Epub 2020 Jun 9.

Abstract

Purpose: Disturbances that affect the inside of the eyeball tend to be highly harmful since they compromise the homeostasis of this organ. Alongside this, the eyeball has several anatomical barriers that prevent the entry of substances. This way, diseases that affect the retina are among those that present greater difficulty in the treatment. In many cases, abnormal proliferation of blood vessels (neovascularization) occurs from the lower layers of the retina. This process damages its structure physiologically and anatomically, causing the rapid and irreversible loss of visual capacity. This work aims to develop nanosuspensions of quantum dots (QDs) conjugated to bevacizumab. Methods: Two types of QDs were produced by aqueous route, stabilized with chitosan conjugated to bevacizumab. The antiangiogenic activity was evaluated in the chorioallantoic membrane model, in which results indicated discrete activity at the doses tested. Samples were assessed for their biosafety in animals, after intravitreal administration, by means of electroretinography (ERG), intraocular pressure (IOP) measurement, histological, morphometric, and immunohistochemical evaluation. Results: No significant alterations were detected in ERG that suggests damage to retinal function by the samples. No significant changes in IOP were also detected. The histological sections did not show signs of acute inflammation, although there was evidence of late retinal damage. The immunohistochemical analysis did not detect any apoptotic bodies. Conclusion: Preliminary results suggest that QDs present potential applicability in ocular therapy, and it is necessary to better characterize their in vivo behavior and to optimize their dosage.

Keywords: VEGF; angiogenesis; electroretinogram; immunohistochemistry; neovascularization; retina.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis Inhibitors / administration & dosage
  • Angiogenesis Inhibitors / pharmacology*
  • Angiogenesis Inhibitors / therapeutic use
  • Animals
  • Bevacizumab / administration & dosage
  • Bevacizumab / pharmacology*
  • Bevacizumab / therapeutic use
  • Chorioallantoic Membrane / drug effects
  • Containment of Biohazards / standards
  • Electroretinography / methods
  • Immunohistochemistry / methods
  • Intraocular Pressure / drug effects
  • Intravitreal Injections
  • Male
  • Models, Animal
  • Nanoparticles / chemistry
  • Nanoparticles / therapeutic use
  • Neovascularization, Pathologic / diagnosis
  • Neovascularization, Pathologic / drug therapy
  • Quantum Dots / administration & dosage
  • Quantum Dots / chemistry
  • Quantum Dots / therapeutic use*
  • Rats
  • Retina / pathology*
  • Retinal Degeneration / diagnosis
  • Retinal Degeneration / metabolism
  • Suspensions / administration & dosage
  • Suspensions / chemistry
  • Suspensions / pharmacokinetics
  • Tumor Necrosis Factor Ligand Superfamily Member 15 / pharmacology
  • Vascular Endothelial Growth Factor A / immunology

Substances

  • Angiogenesis Inhibitors
  • Suspensions
  • TNFSF15 protein, human
  • Tumor Necrosis Factor Ligand Superfamily Member 15
  • Vascular Endothelial Growth Factor A
  • Bevacizumab