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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Dove Medical Press
2017
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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) |
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LDH nanoparticles LDH nanosheets Ocular drug delivery Human corneal epithelial primary cell (HCEpic) Retinal pigment cell (ARPE-19) Active targeting Medicine (General) R5-920 |
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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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