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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| Format: | Article |
| Language: | English |
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Dove Medical Press
2016-07-01
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| Series: | International Journal of Nanomedicine |
| Subjects: | |
| Online Access: | https://www.dovepress.com/therapeutic-effect-of-apatinib-loaded-nanoparticles-on-diabetes-induce-peer-reviewed-article-IJN |
| _version_ | 1818695215001632768 |
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| author | Jeong JH Nguyen HK Lee JE Suh W |
| author_facet | Jeong JH Nguyen HK Lee JE Suh W |
| author_sort | Jeong JH |
| collection | DOAJ |
| 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 |
| first_indexed | 2024-12-17T13:41:55Z |
| format | Article |
| id | doaj.art-ddc69a482ee34378ab6f3a38ad1b3c27 |
| institution | Directory Open Access Journal |
| issn | 1178-2013 |
| language | English |
| last_indexed | 2024-12-17T13:41:55Z |
| publishDate | 2016-07-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | International Journal of Nanomedicine |
| spelling | doaj.art-ddc69a482ee34378ab6f3a38ad1b3c272022-12-21T21:46:16ZengDove Medical PressInternational Journal of Nanomedicine1178-20132016-07-012016default3101310927790Therapeutic effect of apatinib-loaded nanoparticles on diabetes-induced retinal vascular leakageJeong JHNguyen HKLee JESuh WJi 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 factorhttps://www.dovepress.com/therapeutic-effect-of-apatinib-loaded-nanoparticles-on-diabetes-induce-peer-reviewed-article-IJNApatinibdiabetesnanoparticlepermeabilityvascular endothelial growth factor |
| spellingShingle | Jeong JH Nguyen HK Lee JE Suh W Therapeutic effect of apatinib-loaded nanoparticles on diabetes-induced retinal vascular leakage International Journal of Nanomedicine Apatinib diabetes nanoparticle permeability vascular endothelial growth factor |
| title | 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_short | 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 |
| topic | Apatinib diabetes nanoparticle permeability vascular endothelial growth factor |
| url | https://www.dovepress.com/therapeutic-effect-of-apatinib-loaded-nanoparticles-on-diabetes-induce-peer-reviewed-article-IJN |
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