Multifunctional organic–inorganic hybrid nanoparticles and nanosheets based on chitosan derivative and layered double hydroxide: cellular uptake mechanism and application for topical ocular drug delivery

Huibo Chi,1,2,* Yan Gu,1,* Tingting Xu,1 Feng Cao1 1Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Nanjing, 2State Key Laboratory of Drug Delivery Technology and Pharmacokinetics, Tianjin Institute of Pharmaceutical Research Co., Ltd., Tianjin, People’s...

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Autores principales: Chi H, Gu Y, Xu T, Cao F
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Publicado: Dove Medical Press 2017
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spelling oai:doaj.org-article:1591710a89234ca1b3544d9d3b34a5e92021-12-02T00:06:57ZMultifunctional organic–inorganic hybrid nanoparticles and nanosheets based on chitosan derivative and layered double hydroxide: cellular uptake mechanism and application for topical ocular drug delivery1178-2013https://doaj.org/article/1591710a89234ca1b3544d9d3b34a5e92017-02-01T00:00:00Zhttps://www.dovepress.com/multifunctional-organicndashinorganic-hybrid-nanoparticles-and-nanoshe-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Huibo Chi,1,2,* Yan Gu,1,* Tingting Xu,1 Feng Cao1 1Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Nanjing, 2State Key Laboratory of Drug Delivery Technology and Pharmacokinetics, Tianjin Institute of Pharmaceutical Research Co., Ltd., Tianjin, People’s Republic of China *These authors contributed equally to this work Abstract: To study the cellular uptake mechanism of multifunctional organic–inorganic hybrid nanoparticles and nanosheets, new chitosan–glutathione–valine–valine-layered double hydroxide (CG-VV-LDH) nanosheets with active targeting to peptide transporter-1 (PepT-1) were prepared, characterized and further compared with CG-VV-LDH nanoparticles. Both organic–inorganic hybrid nanoparticles and nanosheets showed a sustained release in vitro and prolonged precorneal retention time in vivo, but CG-VV-LDH nanoparticles showed superior permeability in the isolated cornea of rabbits than CG-VV-LDH nanosheets. Furthermore, results of cellular uptake on human corneal epithelial primary cells (HCEpiC) and retinal pigment epithelial (ARPE-19) cells indicated that both clathrin-mediated endocytosis and active transport of PepT-1 are involved in the internalization of CG-VV-LDH nanoparticles and CG-VV-LDH nanosheets. In summary, the CG-VV-LDH nanoparticle may be a promising carrier as a topical ocular drug delivery system for the treatment of ocular diseases of mid-posterior segments, while the CG-VV-LDH nanosheet may be suitable for the treatment of ocular surface diseases. Keywords: LDH nanoparticles, LDH nanosheets, ocular drug delivery, human corneal epithelial primary cell, retinal pigment cell, ARPE-19, active targetingChi HGu YXu TCao FDove Medical PressarticleLDH nanoparticlesLDH nanosheetsOcular drug deliveryHuman corneal epithelial primary cell (HCEpic)Retinal pigment cell (ARPE-19)Active targetingMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 12, Pp 1607-1620 (2017)
institution DOAJ
collection DOAJ
language EN
topic LDH nanoparticles
LDH nanosheets
Ocular drug delivery
Human corneal epithelial primary cell (HCEpic)
Retinal pigment cell (ARPE-19)
Active targeting
Medicine (General)
R5-920
spellingShingle LDH nanoparticles
LDH nanosheets
Ocular drug delivery
Human corneal epithelial primary cell (HCEpic)
Retinal pigment cell (ARPE-19)
Active targeting
Medicine (General)
R5-920
Chi H
Gu Y
Xu T
Cao F
Multifunctional organic–inorganic hybrid nanoparticles and nanosheets based on chitosan derivative and layered double hydroxide: cellular uptake mechanism and application for topical ocular drug delivery
description Huibo Chi,1,2,* Yan Gu,1,* Tingting Xu,1 Feng Cao1 1Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Nanjing, 2State Key Laboratory of Drug Delivery Technology and Pharmacokinetics, Tianjin Institute of Pharmaceutical Research Co., Ltd., Tianjin, People’s Republic of China *These authors contributed equally to this work Abstract: To study the cellular uptake mechanism of multifunctional organic–inorganic hybrid nanoparticles and nanosheets, new chitosan–glutathione–valine–valine-layered double hydroxide (CG-VV-LDH) nanosheets with active targeting to peptide transporter-1 (PepT-1) were prepared, characterized and further compared with CG-VV-LDH nanoparticles. Both organic–inorganic hybrid nanoparticles and nanosheets showed a sustained release in vitro and prolonged precorneal retention time in vivo, but CG-VV-LDH nanoparticles showed superior permeability in the isolated cornea of rabbits than CG-VV-LDH nanosheets. Furthermore, results of cellular uptake on human corneal epithelial primary cells (HCEpiC) and retinal pigment epithelial (ARPE-19) cells indicated that both clathrin-mediated endocytosis and active transport of PepT-1 are involved in the internalization of CG-VV-LDH nanoparticles and CG-VV-LDH nanosheets. In summary, the CG-VV-LDH nanoparticle may be a promising carrier as a topical ocular drug delivery system for the treatment of ocular diseases of mid-posterior segments, while the CG-VV-LDH nanosheet may be suitable for the treatment of ocular surface diseases. Keywords: LDH nanoparticles, LDH nanosheets, ocular drug delivery, human corneal epithelial primary cell, retinal pigment cell, ARPE-19, active targeting
format article
author Chi H
Gu Y
Xu T
Cao F
author_facet Chi H
Gu Y
Xu T
Cao F
author_sort Chi H
title Multifunctional organic–inorganic hybrid nanoparticles and nanosheets based on chitosan derivative and layered double hydroxide: cellular uptake mechanism and application for topical ocular drug delivery
title_short Multifunctional organic–inorganic hybrid nanoparticles and nanosheets based on chitosan derivative and layered double hydroxide: cellular uptake mechanism and application for topical ocular drug delivery
title_full Multifunctional organic–inorganic hybrid nanoparticles and nanosheets based on chitosan derivative and layered double hydroxide: cellular uptake mechanism and application for topical ocular drug delivery
title_fullStr Multifunctional organic–inorganic hybrid nanoparticles and nanosheets based on chitosan derivative and layered double hydroxide: cellular uptake mechanism and application for topical ocular drug delivery
title_full_unstemmed Multifunctional organic–inorganic hybrid nanoparticles and nanosheets based on chitosan derivative and layered double hydroxide: cellular uptake mechanism and application for topical ocular drug delivery
title_sort multifunctional organic–inorganic hybrid nanoparticles and nanosheets based on chitosan derivative and layered double hydroxide: cellular uptake mechanism and application for topical ocular drug delivery
publisher Dove Medical Press
publishDate 2017
url https://doaj.org/article/1591710a89234ca1b3544d9d3b34a5e9
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