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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

Authors Chi H, Gu Y, Xu T, Cao F

Received 3 December 2016

Accepted for publication 27 January 2017

Published 28 February 2017 Volume 2017:12 Pages 1607—1620

DOI https://doi.org/10.2147/IJN.S129311

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Thiruganesh Ramasamy

Peer reviewer comments 3

Editor who approved publication: Dr Lei Yang


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

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