Apatinib-loaded nanoparticles suppress vascular endothelial growth factor-induced angiogenesis and experimental corneal neovascularization

Jung Eun Lee,1,* Koung Li Kim,2,* Danbi Kim,2 Yeongju Yeo,2 Hyounkoo Han,3 Myung Goo Kim,1,4 Sun Hwa Kim,4 Hyuncheol Kim,3,5 Ji Hoon Jeong,1,4 Wonhee Suh2 1School of Pharmacy, Sungkyunkwan University, Suwon, 2College of Pharmacy, Chung-Ang University, Seoul, 3Department of Chemical and Biomolecular...

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Autores principales:	Lee JE, Kim KL, Kim D, Yeo Y, Han H, Kim MG, Kim SH, Kim H, Jeong JH, Suh W
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2017
Materias:	Apatinib corneal neovascularization nanoparticle vascular endothelial growth factor Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/2d8a83a15cb24c6eb445e56e9874659e
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spelling	oai:doaj.org-article:2d8a83a15cb24c6eb445e56e9874659e2021-12-02T05:01:07ZApatinib-loaded nanoparticles suppress vascular endothelial growth factor-induced angiogenesis and experimental corneal neovascularization1178-2013https://doaj.org/article/2d8a83a15cb24c6eb445e56e9874659e2017-07-01T00:00:00Zhttps://www.dovepress.com/apatinib-loaded-nanoparticles-suppress-vascular-endothelial-growth-fac-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Jung Eun Lee,1,* Koung Li Kim,2,* Danbi Kim,2 Yeongju Yeo,2 Hyounkoo Han,3 Myung Goo Kim,1,4 Sun Hwa Kim,4 Hyuncheol Kim,3,5 Ji Hoon Jeong,1,4 Wonhee Suh2 1School of Pharmacy, Sungkyunkwan University, Suwon, 2College of Pharmacy, Chung-Ang University, Seoul, 3Department of Chemical and Biomolecular Engineering, Sogang University, 4Center for Theragnosis Biomedical Research Institute, Korea Institute of Science and Technology (KIST), 5Department of Biomedical Engineering, Sogang University, Seoul, Korea *These authors contributed equally to this work Abstract: Pathological angiogenesis is one of the major symptoms of severe ocular diseases, including corneal neovascularization. The blockade of vascular endothelial growth factor (VEGF) action has been recognized as an efficient strategy for treating corneal neovascularization. In this study, we aimed to investigate whether nanoparticle-based delivery of apatinib, a novel and selective inhibitor of VEGF receptor 2, inhibits VEGF-mediated angiogenesis and suppresses experimental corneal neovascularization. Water-insoluble apatinib was encapsulated in nanoparticles composed of human serum albumin (HSA)-conjugated polyethylene glycol (PEG). In vitro angiogenesis assays showed that apatinib-loaded HSA-PEG (Apa-HSA-PEG) nanoparticles potently inhibited VEGF-induced tube formation, scratch wounding migration, and proliferation of human endothelial cells. In a rat model of alkali burn injury-induced corneal neovascularization, a subconjunctival injection of Apa-HSA-PEG nanoparticles induced a significant decrease in neovascularization compared to that observed with an injection of free apatinib solution or phosphate-buffered saline. An in vivo distribution study using HSA-PEG nanoparticles loaded with fluorescent hydrophobic model drugs revealed the presence of a substantial number of nanoparticles in the corneal stroma within 24 h after injection. These in vitro and in vivo results demonstrate that apatinib-loaded nanoparticles may be promising for the prevention and treatment of corneal neovascularization-related ocular disorders. Keywords: apatinib, corneal neovascularization, nanoparticle, vascular endothelial growth factorLee JEKim KLKim DYeo YHan HKim MGKim SHKim HJeong JHSuh WDove Medical PressarticleApatinibcorneal neovascularizationnanoparticlevascular endothelial growth factorMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 12, Pp 4813-4822 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Apatinib corneal neovascularization nanoparticle vascular endothelial growth factor Medicine (General) R5-920
spellingShingle	Apatinib corneal neovascularization nanoparticle vascular endothelial growth factor Medicine (General) R5-920 Lee JE Kim KL Kim D Yeo Y Han H Kim MG Kim SH Kim H Jeong JH Suh W Apatinib-loaded nanoparticles suppress vascular endothelial growth factor-induced angiogenesis and experimental corneal neovascularization
description	Jung Eun Lee,1,* Koung Li Kim,2,* Danbi Kim,2 Yeongju Yeo,2 Hyounkoo Han,3 Myung Goo Kim,1,4 Sun Hwa Kim,4 Hyuncheol Kim,3,5 Ji Hoon Jeong,1,4 Wonhee Suh2 1School of Pharmacy, Sungkyunkwan University, Suwon, 2College of Pharmacy, Chung-Ang University, Seoul, 3Department of Chemical and Biomolecular Engineering, Sogang University, 4Center for Theragnosis Biomedical Research Institute, Korea Institute of Science and Technology (KIST), 5Department of Biomedical Engineering, Sogang University, Seoul, Korea *These authors contributed equally to this work Abstract: Pathological angiogenesis is one of the major symptoms of severe ocular diseases, including corneal neovascularization. The blockade of vascular endothelial growth factor (VEGF) action has been recognized as an efficient strategy for treating corneal neovascularization. In this study, we aimed to investigate whether nanoparticle-based delivery of apatinib, a novel and selective inhibitor of VEGF receptor 2, inhibits VEGF-mediated angiogenesis and suppresses experimental corneal neovascularization. Water-insoluble apatinib was encapsulated in nanoparticles composed of human serum albumin (HSA)-conjugated polyethylene glycol (PEG). In vitro angiogenesis assays showed that apatinib-loaded HSA-PEG (Apa-HSA-PEG) nanoparticles potently inhibited VEGF-induced tube formation, scratch wounding migration, and proliferation of human endothelial cells. In a rat model of alkali burn injury-induced corneal neovascularization, a subconjunctival injection of Apa-HSA-PEG nanoparticles induced a significant decrease in neovascularization compared to that observed with an injection of free apatinib solution or phosphate-buffered saline. An in vivo distribution study using HSA-PEG nanoparticles loaded with fluorescent hydrophobic model drugs revealed the presence of a substantial number of nanoparticles in the corneal stroma within 24 h after injection. These in vitro and in vivo results demonstrate that apatinib-loaded nanoparticles may be promising for the prevention and treatment of corneal neovascularization-related ocular disorders. Keywords: apatinib, corneal neovascularization, nanoparticle, vascular endothelial growth factor
format	article
author	Lee JE Kim KL Kim D Yeo Y Han H Kim MG Kim SH Kim H Jeong JH Suh W
author_facet	Lee JE Kim KL Kim D Yeo Y Han H Kim MG Kim SH Kim H Jeong JH Suh W
author_sort	Lee JE
title	Apatinib-loaded nanoparticles suppress vascular endothelial growth factor-induced angiogenesis and experimental corneal neovascularization
title_short	Apatinib-loaded nanoparticles suppress vascular endothelial growth factor-induced angiogenesis and experimental corneal neovascularization
title_full	Apatinib-loaded nanoparticles suppress vascular endothelial growth factor-induced angiogenesis and experimental corneal neovascularization
title_fullStr	Apatinib-loaded nanoparticles suppress vascular endothelial growth factor-induced angiogenesis and experimental corneal neovascularization
title_full_unstemmed	Apatinib-loaded nanoparticles suppress vascular endothelial growth factor-induced angiogenesis and experimental corneal neovascularization
title_sort	apatinib-loaded nanoparticles suppress vascular endothelial growth factor-induced angiogenesis and experimental corneal neovascularization
publisher	Dove Medical Press
publishDate	2017
url	https://doaj.org/article/2d8a83a15cb24c6eb445e56e9874659e
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Apatinib-loaded nanoparticles suppress vascular endothelial growth factor-induced angiogenesis and experimental corneal neovascularization

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