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基于壳聚糖衍生物和层状双氢氧化物的多功能有机-无机杂化纳米颗粒和纳米片：细胞摄取机制及在眼部局部给药中的应用

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.

作者信息

Chi Huibo, Gu Yan, Xu Tingting, Cao Feng

机构信息

Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Nanjing; State Key Laboratory of Drug Delivery Technology and Pharmacokinetics, Tianjin Institute of Pharmaceutical Research Co., Ltd., Tianjin, People's Republic of China.

Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Nanjing.

出版信息

Int J Nanomedicine. 2017 Feb 28;12:1607-1620. doi: 10.2147/IJN.S129311. eCollection 2017.

DOI:10.2147/IJN.S129311
PMID:28280329
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5339005/
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.

摘要

为研究多功能有机-无机杂化纳米颗粒和纳米片的细胞摄取机制，制备了对肽转运体-1（PepT-1）具有主动靶向作用的新型壳聚糖-谷胱甘肽-缬氨酸-缬氨酸层状双氢氧化物（CG-VV-LDH）纳米片，对其进行了表征，并与CG-VV-LDH纳米颗粒进行了进一步比较。有机-无机杂化纳米颗粒和纳米片在体外均表现出缓释特性，在体内均具有延长的角膜前滞留时间，但CG-VV-LDH纳米颗粒在兔离体角膜中的通透性优于CG-VV-LDH纳米片。此外，对人角膜上皮原代细胞（HCEpiC）和视网膜色素上皮（ARPE-19）细胞的细胞摄取结果表明，网格蛋白介导的内吞作用和PepT-1的主动转运均参与了CG-VV-LDH纳米颗粒和CG-VV-LDH纳米片的内化过程。综上所述，CG-VV-LDH纳米颗粒作为一种用于治疗眼后段眼部疾病的局部眼用药物递送系统可能是一种有前景的载体，而CG-VV-LDH纳米片可能适用于治疗眼表疾病。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6fc/5339005/a69997918a8a/ijn-12-1607Fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6fc/5339005/71d90c486d9b/ijn-12-1607Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6fc/5339005/f1fba14709d7/ijn-12-1607Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6fc/5339005/c3c19bccdd08/ijn-12-1607Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6fc/5339005/605865768648/ijn-12-1607Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6fc/5339005/33db3d93b528/ijn-12-1607Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6fc/5339005/9ab6743f9fd2/ijn-12-1607Fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6fc/5339005/a69997918a8a/ijn-12-1607Fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6fc/5339005/71d90c486d9b/ijn-12-1607Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6fc/5339005/f1fba14709d7/ijn-12-1607Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6fc/5339005/c3c19bccdd08/ijn-12-1607Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6fc/5339005/605865768648/ijn-12-1607Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6fc/5339005/33db3d93b528/ijn-12-1607Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6fc/5339005/9ab6743f9fd2/ijn-12-1607Fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6fc/5339005/a69997918a8a/ijn-12-1607Fig7.jpg

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