Therapeutic effect of apatinib-loaded nanoparticles on diabetes-induced retinal vascular leakage

Ji Hoon Jeong,1,* Hong Khanh Nguyen,2,* Jung Eun Lee,1 Wonhee Suh2 1School of Pharmacy, Sungkyunkwan University, Suwon, 2College of Pharmacy, Chung-Ang University, Seoul, Korea *These authors contributed equally to this work Abstract: Apatinib, a novel and selective inhibitor of vascular...

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Autores principales:	Jeong JH, Nguyen HK, Lee JE, Suh W
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2016
Materias:	Apatinib diabetes nanoparticle permeability vascular endothelial growth factor Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/ddc69a482ee34378ab6f3a38ad1b3c27
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spelling	oai:doaj.org-article:ddc69a482ee34378ab6f3a38ad1b3c272021-12-02T01:04:56ZTherapeutic effect of apatinib-loaded nanoparticles on diabetes-induced retinal vascular leakage1178-2013https://doaj.org/article/ddc69a482ee34378ab6f3a38ad1b3c272016-07-01T00:00:00Zhttps://www.dovepress.com/therapeutic-effect-of-apatinib-loaded-nanoparticles-on-diabetes-induce-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Ji Hoon Jeong,1,* Hong Khanh Nguyen,2,* Jung Eun Lee,1 Wonhee Suh2 1School of Pharmacy, Sungkyunkwan University, Suwon, 2College of Pharmacy, Chung-Ang University, Seoul, Korea *These authors contributed equally to this work Abstract: Apatinib, a novel and selective inhibitor of vascular endothelial growth factor (VEGF) receptor 2, has been demonstrated recently to exhibit anticancer efficacy by inhibiting the VEGF signaling pathway. Given the importance of VEGF in retinal vascular leakage, the present study was designed to investigate whether apatinib-loaded polymeric nanoparticles inhibit VEGF-mediated retinal vascular hyperpermeability and block diabetes-induced retinal vascular leakage. For the delivery of water-insoluble apatinib, the drug was encapsulated in nanoparticles composed of human serum albumin (HSA)-conjugated polyethylene glycol (PEG). In vitro paracellular permeability and transendothelial electric resistance assays showed that apatinib-loaded HSA-PEG (Apa-HSA-PEG) nanoparticles significantly inhibited VEGF-induced endothelial hyperpermeability in human retinal microvascular endothelial cells. In addition, they substantially reduced the VEGF-induced junctional loss and internalization of vascular endothelial-cadherin, a major component of endothelial junction complexes. In vivo intravitreal injection of Apa-HSA-PEG nanoparticles in mice blocked VEGF-induced retinal vascular leakage. These in vitro and in vivo data indicated that Apa-HSA-PEG nanoparticles efficiently blocked VEGF-induced breakdown of the blood–retinal barrier. In vivo experiments with streptozotocin-induced diabetic mice showed that an intravitreal injection of Apa-HSA-PEG nanoparticles substantially inhibited diabetes-induced retinal vascular leakage. These results demonstrated, for the first time, that apatinib-loaded nanoparticles may be a promising therapeutic agent for the prevention and treatment of diabetes-induced retinal vascular disorders. Keywords: permeability, retinal vascular endothelial cells, vascular endothelial growth factorJeong JHNguyen HKLee JESuh WDove Medical PressarticleApatinibdiabetesnanoparticlepermeabilityvascular endothelial growth factorMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2016, Iss default, Pp 3101-3109 (2016)
institution	DOAJ
collection	DOAJ
language	EN
topic	Apatinib diabetes nanoparticle permeability vascular endothelial growth factor Medicine (General) R5-920
spellingShingle	Apatinib diabetes nanoparticle permeability vascular endothelial growth factor Medicine (General) R5-920 Jeong JH Nguyen HK Lee JE Suh W Therapeutic effect of apatinib-loaded nanoparticles on diabetes-induced retinal vascular leakage
description	Ji Hoon Jeong,1,* Hong Khanh Nguyen,2,* Jung Eun Lee,1 Wonhee Suh2 1School of Pharmacy, Sungkyunkwan University, Suwon, 2College of Pharmacy, Chung-Ang University, Seoul, Korea *These authors contributed equally to this work Abstract: Apatinib, a novel and selective inhibitor of vascular endothelial growth factor (VEGF) receptor 2, has been demonstrated recently to exhibit anticancer efficacy by inhibiting the VEGF signaling pathway. Given the importance of VEGF in retinal vascular leakage, the present study was designed to investigate whether apatinib-loaded polymeric nanoparticles inhibit VEGF-mediated retinal vascular hyperpermeability and block diabetes-induced retinal vascular leakage. For the delivery of water-insoluble apatinib, the drug was encapsulated in nanoparticles composed of human serum albumin (HSA)-conjugated polyethylene glycol (PEG). In vitro paracellular permeability and transendothelial electric resistance assays showed that apatinib-loaded HSA-PEG (Apa-HSA-PEG) nanoparticles significantly inhibited VEGF-induced endothelial hyperpermeability in human retinal microvascular endothelial cells. In addition, they substantially reduced the VEGF-induced junctional loss and internalization of vascular endothelial-cadherin, a major component of endothelial junction complexes. In vivo intravitreal injection of Apa-HSA-PEG nanoparticles in mice blocked VEGF-induced retinal vascular leakage. These in vitro and in vivo data indicated that Apa-HSA-PEG nanoparticles efficiently blocked VEGF-induced breakdown of the blood–retinal barrier. In vivo experiments with streptozotocin-induced diabetic mice showed that an intravitreal injection of Apa-HSA-PEG nanoparticles substantially inhibited diabetes-induced retinal vascular leakage. These results demonstrated, for the first time, that apatinib-loaded nanoparticles may be a promising therapeutic agent for the prevention and treatment of diabetes-induced retinal vascular disorders. Keywords: permeability, retinal vascular endothelial cells, vascular endothelial growth factor
format	article
author	Jeong JH Nguyen HK Lee JE Suh W
author_facet	Jeong JH Nguyen HK Lee JE Suh W
author_sort	Jeong JH
title	Therapeutic effect of apatinib-loaded nanoparticles on diabetes-induced retinal vascular leakage
title_short	Therapeutic effect of apatinib-loaded nanoparticles on diabetes-induced retinal vascular leakage
title_full	Therapeutic effect of apatinib-loaded nanoparticles on diabetes-induced retinal vascular leakage
title_fullStr	Therapeutic effect of apatinib-loaded nanoparticles on diabetes-induced retinal vascular leakage
title_full_unstemmed	Therapeutic effect of apatinib-loaded nanoparticles on diabetes-induced retinal vascular leakage
title_sort	therapeutic effect of apatinib-loaded nanoparticles on diabetes-induced retinal vascular leakage
publisher	Dove Medical Press
publishDate	2016
url	https://doaj.org/article/ddc69a482ee34378ab6f3a38ad1b3c27
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Therapeutic effect of apatinib-loaded nanoparticles on diabetes-induced retinal vascular leakage

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