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

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Miyagawa, T, Chen, Z-Y, Chang, C-Y, Chen, K-H, Wang, Y-K, Liu, G-S ORCID: 0000-0003-3379-724X and Tseng, C-L 2020 , 'Topical application of hyaluronic acid-RGD peptide-coated gelatin/epigallocatechin-3 gallate (EGCG) nanoparticles inhibits corneal neovascularization via inhibition of VEGF production' , Pharmaceutics, vol. 12, no. 5 , pp. 1-17 , doi: 10.3390/pharmaceutics12050404.

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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.

Item Type: Article
Authors/Creators:Miyagawa, T and Chen, Z-Y and Chang, C-Y and Chen, K-H and Wang, Y-K and Liu, G-S and Tseng, C-L
Keywords: RGD peptide, anti-angiogenesis, corneal neovascularization (NV), epigallocatechin gallate (EGCG), eye drops, gelatin, hyaluronic acid (HA), nanoparticles, drug delivery
Journal or Publication Title: Pharmaceutics
Publisher: M D P I AG
ISSN: 1999-4923
DOI / ID Number: 10.3390/pharmaceutics12050404
Copyright Information:

© 2020 by the authors. Licensee MDPI, Basel, Switzerland. Licensed under Creative Commons Attribution 4.0 International (CC BY 4.0) http://creativecommons.org/licenses/by/4.0/

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