Journal
ACTA BIOMATERIALIA
Volume 8, Issue 11, Pages 3932-3940Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.actbio.2012.07.016
Keywords
Flt1 peptide; Genistein; Hyaluronate; Corneal neovascularization; Diabetic retinopathy
Funding
- Korea Healthcare Technology R&D Project, Ministry of Health & Welfare, Republic of Korea [A080711]
- NRF
- MEST [2009-0084578]
- National Research Foundation of Korea [2009-0084578] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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Flt1 peptide of GNQWFI is an antagonistic peptide for vascular endothelial growth factor receptor 1 (VEGFR1 or Flt1). In this work, Fin 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 24 h. 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. (C) 2012 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
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