@article{9d741de86df14cc085d4442899db4373,
title = "Topical application of hyaluronic acid-RGD peptide-coated gelatin/epigallocatechin-3 gallate (EGCG) nanoparticles inhibits corneal neovascularization via inhibition of VEGF production",
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 = "Anti-angiogenesis, Corneal neovascularization (NV), Epigallocatechin gallate (EGCG), Eye drops, Gelatin, Hyaluronic acid (HA), Nanoparticles, RGD peptide",
author = "Takuya Miyagawa and Chen, {Zhi Yu} and Chang, {Che Yi} and Chen, {Ko Hua} and Wang, {Yang Kao} and Liu, {Guei Sheung} and Tseng, {Ching Li}",
note = "Funding Information: Funding: This work was supported by grants from the integrated research grant in health and medical sciences from National Health Research Institute, Taiwan (NHRI-EX105-10334EI), the Ministry of Science and Technology, Taiwan (MOST 106-2628-E-038-001-MY3) and the National Health and Medical Research Council Funding Information: This work was supported by grants from the integrated research grant in health and medical sciences from National Health Research Institute, Taiwan (NHRI-EX105-10334EI), the Ministry of Science and Technology, Taiwan (MOST 106-2628-E-038-001-MY3) and the National Health and Medical Research Council of Australia (GNT1185600). Publisher Copyright: {\textcopyright} 2020 by the authors. Licensee MDPI, Basel, Switzerland.",
year = "2020",
month = apr,
day = "28",
doi = "10.3390/pharmaceutics12050404",
language = "English",
volume = "12",
journal = "Pharmaceutics",
issn = "1999-4923",
publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",
number = "5",
}