Topical ocular delivery to laser-induced choroidal neovascularization by dual internalizing RGD and TAT peptide-modified nanoparticles

Yongchao Chu,1,* Ning Chen,2,* Huajun Yu,2,* Hongjie Mu,1 Bin He,1 Hongchen Hua,1 Aiping Wang,1 Kaoxiang Sun1 1School of Pharmacy, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Key Laboratory of Molecular Pharmacology and Drug Evalua...

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Autores principales:	Chu YC, Chen N, Yu HJ, Mu HJ, He B, Hua HC, Wang AP, Sun KX
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2017
Materias:	nanoparticles ocular drug delivery choroidal neovascularization RGD cell penetrating peptides Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/0b785222c6ff42fba0888a7c394a2c25
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spelling	oai:doaj.org-article:0b785222c6ff42fba0888a7c394a2c252021-12-02T05:10:42ZTopical ocular delivery to laser-induced choroidal neovascularization by dual internalizing RGD and TAT peptide-modified nanoparticles1178-2013https://doaj.org/article/0b785222c6ff42fba0888a7c394a2c252017-02-01T00:00:00Zhttps://www.dovepress.com/topical-ocular-delivery-to-laser-induced-choroidal-neovascularization--peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Yongchao Chu,1,* Ning Chen,2,* Huajun Yu,2,* Hongjie Mu,1 Bin He,1 Hongchen Hua,1 Aiping Wang,1 Kaoxiang Sun1 1School of Pharmacy, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Key Laboratory of Molecular Pharmacology and Drug Evaluation, Ministry of Education, Yantai University, Yantai, Shandong, People’s Republic of China; 2Department of Ophthalmology, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shandong, People’s Republic of China *These authors contributed equally to this work Abstract: A nanoparticle (NP) was developed to target choroidal neovascularization (CNV) via topical ocular administration. The NPs were prepared through conjugation of internalizing arginine-glycine-aspartic acid RGD (iRGD; Ac-CCRGDKGPDC) and transactivated transcription (TAT) (RKKRRQRRRC) peptide to polymerized ethylene glycol and lactic-co-glycolic acid. The iRGD sequence can specifically bind with integrin αvβ3, while TAT facilitates penetration through the ocular barrier. 1H nuclear magnetic resonance and high-performance liquid chromatography demonstrated that up to 80% of iRGD and TAT were conjugated to poly(ethylene glycol)–poly(lactic-co-glycolic acid). The resulting particle size was 67.0±1.7 nm, and the zeta potential of the particles was −6.63±0.43 mV. The corneal permeation of iRGD and TAT NPs increased by 5.50- and 4.56-fold compared to that of bare and iRGD-modified NPs, respectively. Cellular uptake showed that the red fluorescence intensity of iRGD and TAT NPs was highest among primary NPs and iRGD- or TAT-modified NPs. CNV was fully formed 14 days after photocoagulation in Brown Norway (BN) rats as shown by optical coherence tomography and fundus fluorescein angiography analyses. Choroidal flat mounts in BN rats showed that the red fluorescence intensity of NPs followed the order of iRGD and TAT NPs > TAT-modified NPs > iRGD-modified NPs > primary NPs. iRGD and TAT dual-modified NPs thus displayed significant targeting and penetration ability both in vitro and in vivo, indicating that it is a promising drug delivery system for managing CNV via topical ocular administration. Keywords: nanoparticles, ocular drug delivery, choroidal neovascularization, RGD, cell-penetrating peptidesChu YCChen NYu HJMu HJHe BHua HCWang APSun KXDove Medical Pressarticlenanoparticlesocular drug deliverychoroidal neovascularizationRGDcell penetrating peptidesMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 12, Pp 1353-1368 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	nanoparticles ocular drug delivery choroidal neovascularization RGD cell penetrating peptides Medicine (General) R5-920
spellingShingle	nanoparticles ocular drug delivery choroidal neovascularization RGD cell penetrating peptides Medicine (General) R5-920 Chu YC Chen N Yu HJ Mu HJ He B Hua HC Wang AP Sun KX Topical ocular delivery to laser-induced choroidal neovascularization by dual internalizing RGD and TAT peptide-modified nanoparticles
description	Yongchao Chu,1,* Ning Chen,2,* Huajun Yu,2,* Hongjie Mu,1 Bin He,1 Hongchen Hua,1 Aiping Wang,1 Kaoxiang Sun1 1School of Pharmacy, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Key Laboratory of Molecular Pharmacology and Drug Evaluation, Ministry of Education, Yantai University, Yantai, Shandong, People’s Republic of China; 2Department of Ophthalmology, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shandong, People’s Republic of China *These authors contributed equally to this work Abstract: A nanoparticle (NP) was developed to target choroidal neovascularization (CNV) via topical ocular administration. The NPs were prepared through conjugation of internalizing arginine-glycine-aspartic acid RGD (iRGD; Ac-CCRGDKGPDC) and transactivated transcription (TAT) (RKKRRQRRRC) peptide to polymerized ethylene glycol and lactic-co-glycolic acid. The iRGD sequence can specifically bind with integrin αvβ3, while TAT facilitates penetration through the ocular barrier. 1H nuclear magnetic resonance and high-performance liquid chromatography demonstrated that up to 80% of iRGD and TAT were conjugated to poly(ethylene glycol)–poly(lactic-co-glycolic acid). The resulting particle size was 67.0±1.7 nm, and the zeta potential of the particles was −6.63±0.43 mV. The corneal permeation of iRGD and TAT NPs increased by 5.50- and 4.56-fold compared to that of bare and iRGD-modified NPs, respectively. Cellular uptake showed that the red fluorescence intensity of iRGD and TAT NPs was highest among primary NPs and iRGD- or TAT-modified NPs. CNV was fully formed 14 days after photocoagulation in Brown Norway (BN) rats as shown by optical coherence tomography and fundus fluorescein angiography analyses. Choroidal flat mounts in BN rats showed that the red fluorescence intensity of NPs followed the order of iRGD and TAT NPs > TAT-modified NPs > iRGD-modified NPs > primary NPs. iRGD and TAT dual-modified NPs thus displayed significant targeting and penetration ability both in vitro and in vivo, indicating that it is a promising drug delivery system for managing CNV via topical ocular administration. Keywords: nanoparticles, ocular drug delivery, choroidal neovascularization, RGD, cell-penetrating peptides
format	article
author	Chu YC Chen N Yu HJ Mu HJ He B Hua HC Wang AP Sun KX
author_facet	Chu YC Chen N Yu HJ Mu HJ He B Hua HC Wang AP Sun KX
author_sort	Chu YC
title	Topical ocular delivery to laser-induced choroidal neovascularization by dual internalizing RGD and TAT peptide-modified nanoparticles
title_short	Topical ocular delivery to laser-induced choroidal neovascularization by dual internalizing RGD and TAT peptide-modified nanoparticles
title_full	Topical ocular delivery to laser-induced choroidal neovascularization by dual internalizing RGD and TAT peptide-modified nanoparticles
title_fullStr	Topical ocular delivery to laser-induced choroidal neovascularization by dual internalizing RGD and TAT peptide-modified nanoparticles
title_full_unstemmed	Topical ocular delivery to laser-induced choroidal neovascularization by dual internalizing RGD and TAT peptide-modified nanoparticles
title_sort	topical ocular delivery to laser-induced choroidal neovascularization by dual internalizing rgd and tat peptide-modified nanoparticles
publisher	Dove Medical Press
publishDate	2017
url	https://doaj.org/article/0b785222c6ff42fba0888a7c394a2c25
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Topical ocular delivery to laser-induced choroidal neovascularization by dual internalizing RGD and TAT peptide-modified nanoparticles

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