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Drug Delivery Volume 25 ,Issue 1 ,2018-01-01
Hyaluronic acid modified MPEG-b-PAE block copolymer aqueous micelles for efficient ophthalmic drug delivery of hydrophobic genistein
Research Article
Cong Li 1 Rui Chen 2 , 3 Mengzhen Xu 2 Jiyan Qiao 2 Liang Yan 4 Xin Dong Guo 1
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Received 2018-4-9, accepted for publication 2018-5-7, Published 2018-5-7

The ophthalmic drug delivery is a challenge in the clinical treatment of ocular diseases. The traditional drug administration usually shows apparent limitations, such as the low bioavailability from the reason of low penetration of the cornea and the short survival time of drug in the eyes. To overcome these shortcomings, we propose an amphiphilic polymer micelle modified with hyaluronic acid (HA) for high efficient ophthalmic delivery of genistein, a widely used hydrophobic drug for treatment of ocular angiogenesis. The MPEG-b-PAE copolymer was synthesized by the Michael addition reaction, and the final drug carrier MPEG-b-PAE-g-HA was obtained by the process of esterification. Then, genistein was packaged in this drug carrier, getting the final micelles with size of about 84.5 nm. The cell viability tests showed that the micelles take no obvious cytotoxicity to the human cornea epithelium cells. The functionalities of drug slow release and cornea penetration ability were demonstrated in a series ex vivo experiments. Further, the vascular inhibition test illustrated that the micelles could significantly inhibit the angiogenesis of human umbilical vein endothelial cells. These results indicate that the constructed polymer has high feasibility to be used as drug carrier in the treatment of ocular diseases.


neovascularization inhibition;cornea penetration;ocular delivery;genistein;Polymer micelles


© 2018 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Schematic illustration for the synthetic route of MPEG-b-PAE-g-HA copolymer.

(a) 1H NMR spectra of MPEG (black line), MPEG-A (red line) in d-CDCl3. (b) 1H NMR spectra of MPEG-b-PAE in d-CDCl3. (c) 1H NMR spectrum of MPEG-b-PAE-g-HA in D2O. (d) GPC spectrum of MPEG-b-PAE-g-HA.

(a) TEM image of genistein/MPEG-b-PAE-g-HA micelles. (b) Particle size and (c) Zeta potential results of genistein/MPEG-b-PAE-g-HA micelle detected by dynamic light scattering. (d) Ultraviolet spectrophotometer of genistein (blue line), blank micelle (red line) and the drug-loaded micelle (black line).

(a) In vitro drug release curves of drug-loading micelle and pure Genistein (n = 3). (b) In vitro cytotoxicity of the genistein/MPEG-b-PAE-g-HA micelles against HCECs after incubation for 24 h, 48 h, and 72 h (n = 5).

(a) In vitro corneal cumulative penetration profiles of genistein/MPEG-b-PAE-g-HA micelles and genistein eye drops. (b) The numbers of neovascular lumens of control groups and micelle treatment groups, n = 5. (c) Neovascular lumens formed by control HUVECs. (d) Vascular inhibition of genistein/MPEG-b-PAE-g-HA micelles on HUVECs.


1. Rui Chen.CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology, Beijing, China;Laboratory of Molecular Toxicology, State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.chenr@nanoctr.cn
2. Xin Dong Guo.Beijing Laboratory of Biomedical Materials, College of Materials Science and Engineering, Beijing University of Chemical Technology, Beijing, China.xdguo@buct.edu.cn


Cong Li,Rui Chen,Mengzhen Xu,Jiyan Qiao,Liang Yan,Xin Dong Guo. Hyaluronic acid modified MPEG-b-PAE block copolymer aqueous micelles for efficient ophthalmic drug delivery of hydrophobic genistein. Drug Delivery ,Vol.25, Issue 1(2018)



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