Anti-Angiogenic Activity Of Bevacizumab-Bearing Dexamethasone-Loaded PLGA Nanoparticles For Potential Intravitreal Applications

Jiaxin Liu, Xueyan Zhang, Ge Li, Fei Xu, Shuang Li, Lesheng Teng, Youxin Li, Fengying Sun School of Life Sciences, Jilin University, Changchun, Jilin, People’s Republic of ChinaCorrespondence: Youxin Li; Fengying SunSchool of Life Sciences, Jilin University, 2699 Qianjin Street, Changchun,...

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Autores principales:	Liu J, Zhang X, Li G, Xu F, Li S, Teng L, Li Y, Sun F
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2019
Materias:	nanoparticles dexamethasone bevacizumab anti-angiogenesis vegf Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/d479c0ab0b8f4c3d92d6e2d5d758c1b1
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spelling	oai:doaj.org-article:d479c0ab0b8f4c3d92d6e2d5d758c1b12021-12-02T06:56:19ZAnti-Angiogenic Activity Of Bevacizumab-Bearing Dexamethasone-Loaded PLGA Nanoparticles For Potential Intravitreal Applications1178-2013https://doaj.org/article/d479c0ab0b8f4c3d92d6e2d5d758c1b12019-11-01T00:00:00Zhttps://www.dovepress.com/anti-angiogenic-activity-of-bevacizumab-bearing-dexamethasone-loaded-p-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Jiaxin Liu, Xueyan Zhang, Ge Li, Fei Xu, Shuang Li, Lesheng Teng, Youxin Li, Fengying Sun School of Life Sciences, Jilin University, Changchun, Jilin, People’s Republic of ChinaCorrespondence: Youxin Li; Fengying SunSchool of Life Sciences, Jilin University, 2699 Qianjin Street, Changchun, Jilin 130012, People’s Republic of ChinaTel/Fax +86 431 8515 5320Email liyouxin@jlu.edu.cn; sunfengying@jlu.edu.cnPurpose: Age-related macular degeneration is a multifactorial disease involving inflammation and choroidal neovascularization. Vascular endothelial growth factor (VEGF) has been regarded as a potential therapeutic target to treat choroidal neovascularization. Dexamethasone can interfere with the expression or action of VEGF while bevacizumab targets and combines with VEGF. We propose electrostatically-conjugated bevacizumab-bearing dexamethasone-loaded poly (D,L-lactide-co-glycolide)/polyethylenimine nanoparticles (eBev-DPPNs) for angiogenic combination treatment of ocular diseases.Methods: We prepared a novel nanoparticle composed of poly (D, L-lactide-co-glycolide) and polyethylenimine and loaded the nanoparticles with dexamethasone. Bevacizumab was adsorbed onto the surfaces of the nanoparticles by electrostatic interactions. The eBev-DPPNs were evaluated according to their size, polydispersity index, zeta potential, morphology, drug loading, release behavior, and stability. The structural stability of bevacizumab on the surface of the nanoparticles was also analyzed. Subsequently, angiogenesis was investigated in the presence of the eBev-DPPNs using cell apoptosis, wound healing, Transwell invasion, and tube formation assays on the human umbilical vein endothelial cells (HUVECs) in vitro and chick embryo chorioallantoic membrane assay in vivo. The eBev-DPPNs intravitreal injection was applied in the laser-induced rabbit choroidal neovascularization (CNV) model to confirm the role for potential intravitreal applications.Results: The eBev-DPPNs was about 200 nm in diameter, with a narrow diameter distribution, and the surface charge was neutral (0.85 ± 0.37mV), which made the eBev-DPPNs stable under physiological conditions. The apoptosis, migration, invasion, and tube formation assays showed that the eBev-DPPNs had a good anti-angiogenic effect on HUVECs. The eBev-DPPNs also provided a strong inhibitory effect on VEGF secretion from HUVECs. Moreover, in vivo chick embryo chorioallantoic membrane assay showed eBev-DPPNs greatly reduced the amount of blood vessels. The leakage area of CNV decreased in the eBev-DPPNs group on rabbit CNV model.Conclusion: The eBev-DPPNs are a promising novel anti-angiogenesis therapeutic for potential intravitreal applications such as age-related macular degeneration.Keywords: nanoparticles, dexamethasone, bevacizumab, anti-angiogenesis, VEGFLiu JZhang XLi GXu FLi STeng LLi YSun FDove Medical Pressarticlenanoparticlesdexamethasonebevacizumabanti-angiogenesisvegfMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 14, Pp 8819-8834 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	nanoparticles dexamethasone bevacizumab anti-angiogenesis vegf Medicine (General) R5-920
spellingShingle	nanoparticles dexamethasone bevacizumab anti-angiogenesis vegf Medicine (General) R5-920 Liu J Zhang X Li G Xu F Li S Teng L Li Y Sun F Anti-Angiogenic Activity Of Bevacizumab-Bearing Dexamethasone-Loaded PLGA Nanoparticles For Potential Intravitreal Applications
description	Jiaxin Liu, Xueyan Zhang, Ge Li, Fei Xu, Shuang Li, Lesheng Teng, Youxin Li, Fengying Sun School of Life Sciences, Jilin University, Changchun, Jilin, People’s Republic of ChinaCorrespondence: Youxin Li; Fengying SunSchool of Life Sciences, Jilin University, 2699 Qianjin Street, Changchun, Jilin 130012, People’s Republic of ChinaTel/Fax +86 431 8515 5320Email liyouxin@jlu.edu.cn; sunfengying@jlu.edu.cnPurpose: Age-related macular degeneration is a multifactorial disease involving inflammation and choroidal neovascularization. Vascular endothelial growth factor (VEGF) has been regarded as a potential therapeutic target to treat choroidal neovascularization. Dexamethasone can interfere with the expression or action of VEGF while bevacizumab targets and combines with VEGF. We propose electrostatically-conjugated bevacizumab-bearing dexamethasone-loaded poly (D,L-lactide-co-glycolide)/polyethylenimine nanoparticles (eBev-DPPNs) for angiogenic combination treatment of ocular diseases.Methods: We prepared a novel nanoparticle composed of poly (D, L-lactide-co-glycolide) and polyethylenimine and loaded the nanoparticles with dexamethasone. Bevacizumab was adsorbed onto the surfaces of the nanoparticles by electrostatic interactions. The eBev-DPPNs were evaluated according to their size, polydispersity index, zeta potential, morphology, drug loading, release behavior, and stability. The structural stability of bevacizumab on the surface of the nanoparticles was also analyzed. Subsequently, angiogenesis was investigated in the presence of the eBev-DPPNs using cell apoptosis, wound healing, Transwell invasion, and tube formation assays on the human umbilical vein endothelial cells (HUVECs) in vitro and chick embryo chorioallantoic membrane assay in vivo. The eBev-DPPNs intravitreal injection was applied in the laser-induced rabbit choroidal neovascularization (CNV) model to confirm the role for potential intravitreal applications.Results: The eBev-DPPNs was about 200 nm in diameter, with a narrow diameter distribution, and the surface charge was neutral (0.85 ± 0.37mV), which made the eBev-DPPNs stable under physiological conditions. The apoptosis, migration, invasion, and tube formation assays showed that the eBev-DPPNs had a good anti-angiogenic effect on HUVECs. The eBev-DPPNs also provided a strong inhibitory effect on VEGF secretion from HUVECs. Moreover, in vivo chick embryo chorioallantoic membrane assay showed eBev-DPPNs greatly reduced the amount of blood vessels. The leakage area of CNV decreased in the eBev-DPPNs group on rabbit CNV model.Conclusion: The eBev-DPPNs are a promising novel anti-angiogenesis therapeutic for potential intravitreal applications such as age-related macular degeneration.Keywords: nanoparticles, dexamethasone, bevacizumab, anti-angiogenesis, VEGF
format	article
author	Liu J Zhang X Li G Xu F Li S Teng L Li Y Sun F
author_facet	Liu J Zhang X Li G Xu F Li S Teng L Li Y Sun F
author_sort	Liu J
title	Anti-Angiogenic Activity Of Bevacizumab-Bearing Dexamethasone-Loaded PLGA Nanoparticles For Potential Intravitreal Applications
title_short	Anti-Angiogenic Activity Of Bevacizumab-Bearing Dexamethasone-Loaded PLGA Nanoparticles For Potential Intravitreal Applications
title_full	Anti-Angiogenic Activity Of Bevacizumab-Bearing Dexamethasone-Loaded PLGA Nanoparticles For Potential Intravitreal Applications
title_fullStr	Anti-Angiogenic Activity Of Bevacizumab-Bearing Dexamethasone-Loaded PLGA Nanoparticles For Potential Intravitreal Applications
title_full_unstemmed	Anti-Angiogenic Activity Of Bevacizumab-Bearing Dexamethasone-Loaded PLGA Nanoparticles For Potential Intravitreal Applications
title_sort	anti-angiogenic activity of bevacizumab-bearing dexamethasone-loaded plga nanoparticles for potential intravitreal applications
publisher	Dove Medical Press
publishDate	2019
url	https://doaj.org/article/d479c0ab0b8f4c3d92d6e2d5d758c1b1
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Anti-Angiogenic Activity Of Bevacizumab-Bearing Dexamethasone-Loaded PLGA Nanoparticles For Potential Intravitreal Applications

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