Flt1 peptide-hyaluronate conjugate micelle-like nanoparticles encapsulating genistein for the treatment of ocular neovascularization.

Abstract

Flt1 peptide of GNQWFI is an antagonistic peptide for vascular endothelial growth factor receptor 1 (VEGFR1 or Flt1). In this work, Flt1 peptide-hyaluronate (HA) conjugates were successfully synthesized and the resulting micelle-like nanoparticles were exploited to encapsulate genistein, an inhibitor of tyrosine-specific protein kinases, for the treatment of ocular neovascularization. The mean diameter of genistein-loaded Flt1 peptide-HA conjugate micelles was measured to be 172.0±18.7 nm, with a drug-loading efficiency of 40-50%. In vitro release tests of genistein from the genistein-loaded Flt1 peptide-HA conjugate micelles exhibited the controlled release for longer than 24h. In vitro biological activity of genistein/Flt1 peptide-HA micelles was corroborated from the synergistic anti-proliferation of human umbilical vein endothelial cells (HUVECs). Furthermore, we could confirm the anti-angiogenic effect of genistein/Flt1 peptide-HA micelles from the statistically significant suppression of corneal neovascularization in silver nitrate cauterized corneas of SD rats. The retinal vascular hyperpermeability was also drastically reduced by the treatment in diabetic retinopathy model rats.

• Authors: Hyemin Kim, Jun-Sub Choi, Ki Su Kim, Jeong-A Yang, Choun-Ki Joo, Sei Kwang Hahn
• Journal: Acta biomaterialia (Acta Biomater) Vol. 8 Issue 11 Pg. 3932-40 (Nov 2012) ISSN: 1878-7568 [Electronic] England
• PMID: 22824530 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Chemical References

• Angiogenesis Inhibitors
• Micelles
• Peptides
• Hyaluronic Acid
• Genistein
• Vascular Endothelial Growth Factor Receptor-1

Topics

• Amino Acid Sequence
• Angiogenesis Inhibitors (pharmacology, therapeutic use)
• Animals
• Corneal Neovascularization (drug therapy, pathology)
• Diabetic Retinopathy (drug therapy)
• Genistein (pharmacology, therapeutic use)
• Human Umbilical Vein Endothelial Cells
• Humans
• Hyaluronic Acid (chemistry)
• Male
• Micelles
• Microscopy, Electron, Transmission
• Molecular Sequence Data
• Nanoparticles (chemistry, ultrastructure)
• Particle Size
• Peptides (chemistry)
• Permeability (drug effects)
• Rats
• Rats, Sprague-Dawley
• Retina (drug effects, pathology)
• Vascular Endothelial Growth Factor Receptor-1 (chemistry)