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

doi:10.3390/pharmaceutics12050404

Topical Application of Hyaluronic Acid-RGD Peptide-Coated Gelatin/Epigallocatechin-3 Gallate (EGCG) Nanoparticles Inhibits Corneal Neovascularization Via Inhibition of VEGF Production

Pharmaceutics. 2020 Apr 28;12(5):404. doi: 10.3390/pharmaceutics12050404.

Authors

Takuya Miyagawa^{1

2}, Zhi-Yu Chen¹, Che-Yi Chang¹, Ko-Hua Chen^{3

4}, Yang-Kao Wang⁵, Guei-Sheung Liu^{1

6

7}, Ching-Li Tseng^{1

8

9

10}

Affiliations

¹ Graduate Institute of Biomedical Materials and Tissue Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei City 110, Taiwan.
² B CUBE, Center for Molecular Bioengineering, Technische Universität Dresden, Tatzberg 41, 01307 Dresden, Germany.
³ Department of Ophthalmology, Taipei Veterans General Hospital, Taipei City 112, Taiwan.
⁴ Department of Ophthalmology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, 11031, Taiwan.
⁵ Department of Cell Biology and Anatomy, College of Medicine, National Cheng Kung University, Tainan City 701, Taiwan.
⁶ Menzies Institute for Medical Research, University of Tasmania, Hobart, TAS 7000, Australia.
⁷ Ophthalmology, Department of Surgery, University of Melbourne, East Melbourne, VIC 3002, Australia.
⁸ International Ph. D. Program in Biomedical Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei city 110, Taiwan.
⁹ Research Center of Biomedical Device, College of Biomedical Engineering, Taipei Medical University, Taipei city 110, Taiwan.
¹⁰ International Ph. D. Program in Cell Therapy and Regenerative Medicine, College of Medicine, Taipei Medical University, Taipei city 110, Taiwan.

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.

Keywords: RGD peptide; anti-angiogenesis; corneal neovascularization (NV); epigallocatechin gallate (EGCG); eye drops; gelatin; hyaluronic acid (HA), nanoparticles.

Abstract

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