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139225 - Topical application of hyaluronic acid-RGD peptide-coated gelatin.pdf (1.78 MB)

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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posted on 2023-05-20, 14:45 authored by Miyagawa, T, Chen, Z-Y, Chang, C-Y, Chen, K-H, Wang, Y-K, Guei-Sheung LiuGuei-Sheung Liu, Tseng, C-L
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.

History

Publication title

Pharmaceutics

Volume

12

Issue

5

Article number

E404

Number

E404

Pagination

1-17

ISSN

1999-4923

Department/School

Menzies Institute for Medical Research

Publisher

M D P I AG

Place of publication

Switzerland

Rights statement

© 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/

Repository Status

  • Open

Socio-economic Objectives

Clinical health not elsewhere classified; Expanding knowledge in the environmental sciences