Hyaluronic acid modified MPEG-b-PAE block copolymer aqueous micelles for efficient ophthalmic drug delivery of hydrophobic genistein

Drug Delivery

Cong Li¹  Xin Dong Guo¹  Liang Yan²  Jiyan Qiao³  Mengzhen Xu³  Rui Chen⁴ 

[1] Beijing Laboratory of Biomedical Materials, College of Materials Science and Engineering, Beijing University of Chemical Technology, Beijing, China;CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing, Chin;CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology, Beijing, China;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;

关键词: Polymer micelles;    genistein;    ocular delivery;    cornea penetration;    neovascularization inhibition;   

DOI  :  10.1080/10717544.2018.1474972

来源: publisher

【 摘 要 】

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.

【 授权许可】

CC BY