Topical application of hyaluronic acid-RGD peptide-coated gelatin/epigallocatechin-3 gallate (EGCG) nanoparticles inhibits corneal neovascularization via inhibition of VEGF production

Takuya Miyagawa, Zhi Yu Chen, Che Yi Chang, Ko Hua Chen, Yang Kao Wang, Guei Sheung Liu, Ching Li Tseng

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Neovascularization (NV) of the cornea disrupts vision which leads to blindness. Investigation of antiangiogenic, slow-release and biocompatible approaches for treating corneal NV is of great importance. We designed an eye drop formulation containing gelatin/epigallocatechin-3-gallate (EGCG) nanoparticles (NPs) for targeted therapy in corneal NV. Gelatin-EGCG self-assembled NPs with hyaluronic acid (HA) coating on its surface (named GEH) and hyaluronic acid conjugated with arginine-glycine-aspartic acid (RGD) (GEH-RGD) were synthesized. Human umbilical vein endothelial cells (HUVECs) were used to evaluate the antiangiogenic effect of GEH-RGD NPs in vitro. Moreover, a mouse model of chemical corneal cauterization was employed to evaluate the antiangiogenic effects of GEH-RGD NPs in vivo. GEH-RGD NP treatment significantly reduced endothelial cell tube formation and inhibited metalloproteinase (MMP)-2 and MMP-9 activity in HUVECs in vitro. Topical application of GEH-RGD NPs (once daily for a week) significantly attenuated the formation of pathological vessels in the mouse cornea after chemical cauterization. Reduction in both vascular endothelial growth factor (VEGF) and MMP-9 protein in the GEH-RGD NP-treated cauterized corneas was observed. These results confirm the molecular mechanism of the antiangiogenic effect of GEH-RGD NPs in suppressing pathological corneal NV.

Original languageEnglish
Article number404
JournalPharmaceutics
Volume12
Issue number5
DOIs
Publication statusPublished - May 2020

Keywords

  • Anti-angiogenesis
  • Corneal neovascularization (NV)
  • Epigallocatechin gallate (EGCG)
  • Eye drops
  • Gelatin
  • Hyaluronic acid (HA)
  • Nanoparticles
  • RGD peptide

ASJC Scopus subject areas

  • Pharmaceutical Science

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