Poly(lactic-co-glycolic acid) nanoparticle-mediated interleukin-12 delivery for the treatment of diabetic retinopathy

Lina Zeng,1,* Wenbei Ma,1,* Lingyu Shi,1 Xiaohong Chen,1 Rong Wu,1 Yingying Zhang,2 Huaiwen Chen,2 Hui Chen11Department of Ophthalmology, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, People’s Republic of China; 2Sunlipo Biotech Research Center for Nanomedicine, Shangha...

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Autores principales:	Zeng L, Ma W, Shi L, Chen X, Wu R, Zhang Y, Chen H
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2019
Materias:	interleukin-12 nanoparticles angiogenesis controlled release diabetic retinopathy Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/42dfc19cb6d44749bc298306008df7c5
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spelling	oai:doaj.org-article:42dfc19cb6d44749bc298306008df7c52021-12-02T10:44:55ZPoly(lactic-co-glycolic acid) nanoparticle-mediated interleukin-12 delivery for the treatment of diabetic retinopathy1178-2013https://doaj.org/article/42dfc19cb6d44749bc298306008df7c52019-08-01T00:00:00Zhttps://www.dovepress.com/polylactic-co-glycolic-acid-nanoparticle-mediated-interleukin-12-deliv-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Lina Zeng,1,* Wenbei Ma,1,* Lingyu Shi,1 Xiaohong Chen,1 Rong Wu,1 Yingying Zhang,2 Huaiwen Chen,2 Hui Chen11Department of Ophthalmology, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, People’s Republic of China; 2Sunlipo Biotech Research Center for Nanomedicine, Shanghai 201507, People’s Republic of China*These authors contributed equally to this workBackground: Diabetic retinopathy (DR) is a complication of diabetes that affects the eyes and vision. It is a leading cause of visual impairment and blindness in working-age people. Vascular endothelial growth factor-A (VEGF-A) is a primary initiator and potential mediator of DR. Matrix metalloproteinase-9 (MMP-9) plays a progressive role in the onset and severity of DR. Interleukin-12 (IL-12) is a cytokine of the chemokine family that could reduce the levels of MMP-9 and VEGF-A and suppress tumor angiogenesis. We hypothesize that IL-12 may also have superior therapeutic efficacy against DR. However, protein drugs are prone to degradation by various proteases after drug injection. Therefore, they have short half-lives and low blood concentrations. The objective of this study was to develop IL-12-loaded nanoparticles for long-term and sustained DR treatment.Methods: IL-12-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (IL-12-PNP) were developed by double emulsion. The characteristics, anti-DR activity, and mechanisms of IL-12-PNP were examined in vitro and in vivo.Results: The nanoparticles had suitable particle size (&sim;132.8 nm), drug encapsulation efficiency (&sim;34.7%), and sustained drug release profile. Compared with IL-12 and blank nanoparticles, IL-12-PNP showed better inhibitory efficacy against VEGF-A and MMP-9 expression in rat endothelial cells and DR mouse retina. Intraocular IL-12-PNP administration significantly reduced retinal damage in DR mice as they presented with increased thickness and decreased neovascularization after treatment.Conclusion: These data indicate that IL-12-PNP is an effective drug delivery platform for DR therapy. It restores the thickness and reduces neovascularization of the retinas of DR mice.Keywords: interleukin-12, nanoparticles, angiogenesis, controlled release, diabetic retinopathyZeng LMa WShi LChen XWu RZhang YChen HChen HDove Medical Pressarticleinterleukin-12nanoparticlesangiogenesiscontrolled releasediabetic retinopathyMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 14, Pp 6357-6369 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	interleukin-12 nanoparticles angiogenesis controlled release diabetic retinopathy Medicine (General) R5-920
spellingShingle	interleukin-12 nanoparticles angiogenesis controlled release diabetic retinopathy Medicine (General) R5-920 Zeng L Ma W Shi L Chen X Wu R Zhang Y Chen H Chen H Poly(lactic-co-glycolic acid) nanoparticle-mediated interleukin-12 delivery for the treatment of diabetic retinopathy
description	Lina Zeng,1,* Wenbei Ma,1,* Lingyu Shi,1 Xiaohong Chen,1 Rong Wu,1 Yingying Zhang,2 Huaiwen Chen,2 Hui Chen11Department of Ophthalmology, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, People’s Republic of China; 2Sunlipo Biotech Research Center for Nanomedicine, Shanghai 201507, People’s Republic of China*These authors contributed equally to this workBackground: Diabetic retinopathy (DR) is a complication of diabetes that affects the eyes and vision. It is a leading cause of visual impairment and blindness in working-age people. Vascular endothelial growth factor-A (VEGF-A) is a primary initiator and potential mediator of DR. Matrix metalloproteinase-9 (MMP-9) plays a progressive role in the onset and severity of DR. Interleukin-12 (IL-12) is a cytokine of the chemokine family that could reduce the levels of MMP-9 and VEGF-A and suppress tumor angiogenesis. We hypothesize that IL-12 may also have superior therapeutic efficacy against DR. However, protein drugs are prone to degradation by various proteases after drug injection. Therefore, they have short half-lives and low blood concentrations. The objective of this study was to develop IL-12-loaded nanoparticles for long-term and sustained DR treatment.Methods: IL-12-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (IL-12-PNP) were developed by double emulsion. The characteristics, anti-DR activity, and mechanisms of IL-12-PNP were examined in vitro and in vivo.Results: The nanoparticles had suitable particle size (&sim;132.8 nm), drug encapsulation efficiency (&sim;34.7%), and sustained drug release profile. Compared with IL-12 and blank nanoparticles, IL-12-PNP showed better inhibitory efficacy against VEGF-A and MMP-9 expression in rat endothelial cells and DR mouse retina. Intraocular IL-12-PNP administration significantly reduced retinal damage in DR mice as they presented with increased thickness and decreased neovascularization after treatment.Conclusion: These data indicate that IL-12-PNP is an effective drug delivery platform for DR therapy. It restores the thickness and reduces neovascularization of the retinas of DR mice.Keywords: interleukin-12, nanoparticles, angiogenesis, controlled release, diabetic retinopathy
format	article
author	Zeng L Ma W Shi L Chen X Wu R Zhang Y Chen H Chen H
author_facet	Zeng L Ma W Shi L Chen X Wu R Zhang Y Chen H Chen H
author_sort	Zeng L
title	Poly(lactic-co-glycolic acid) nanoparticle-mediated interleukin-12 delivery for the treatment of diabetic retinopathy
title_short	Poly(lactic-co-glycolic acid) nanoparticle-mediated interleukin-12 delivery for the treatment of diabetic retinopathy
title_full	Poly(lactic-co-glycolic acid) nanoparticle-mediated interleukin-12 delivery for the treatment of diabetic retinopathy
title_fullStr	Poly(lactic-co-glycolic acid) nanoparticle-mediated interleukin-12 delivery for the treatment of diabetic retinopathy
title_full_unstemmed	Poly(lactic-co-glycolic acid) nanoparticle-mediated interleukin-12 delivery for the treatment of diabetic retinopathy
title_sort	poly(lactic-co-glycolic acid) nanoparticle-mediated interleukin-12 delivery for the treatment of diabetic retinopathy
publisher	Dove Medical Press
publishDate	2019
url	https://doaj.org/article/42dfc19cb6d44749bc298306008df7c5
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Poly(lactic-co-glycolic acid) nanoparticle-mediated interleukin-12 delivery for the treatment of diabetic retinopathy

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