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纳米聚多巴胺交联巯基功能化透明质酸水凝胶用于血管生成药物传递。

Nano polydopamine crosslinked thiol-functionalized hyaluronic acid hydrogel for angiogenic drug delivery.

机构信息

Centre for Nanosciences and Molecular Medicine, Amrita Institute of Medical Sciences and Research Centre, Amrita Vishwa Vidyapeetham, Kochi, 682041, India.

Centre for Nanosciences and Molecular Medicine, Amrita Institute of Medical Sciences and Research Centre, Amrita Vishwa Vidyapeetham, Kochi, 682041, India.

出版信息

Colloids Surf B Biointerfaces. 2019 May 1;177:41-49. doi: 10.1016/j.colsurfb.2019.01.035. Epub 2019 Jan 22.

DOI:10.1016/j.colsurfb.2019.01.035
PMID:30711759
Abstract

Crosslinking of polymeric network using nanoparticles by physical or chemical method to obtain hydrogel is an emerging approach. Herein, we synthesized Polydopamine (PDA) nanoparticles via oxidative self-polymerization of dopamine in water-ethanol mixture. Thiol-functionalized hyaluronic acid was developed using cysteamine and hyaluronic acid (HA-Cys) via 1-Ethyl-3-(3-Dimethylaminopropyl) Carbodiimide - N-hydroxysuccinimide (EDC-NHS) crosslinking chemistry. Developed HA-Cys conjugate was cross-linked using PDA nanoparticles via Michael-type addition reaction. Synthesized nanoparticles were monodisperse with size of 124 ± 8 nm and had spherical morphology. FTIR characterization confirmed successful synthesis of HA-Cys conjugate and subsequent crosslinking with PDA nanoparticles. Rheological characterization revealed that hydrogels were injectable in nature with good mechanical stability. Dimethyloxalylglycine (DMOG) loaded PDA nanoparticle showed sustained drug release for period of 7 days from composite hydrogel. Hydrogel microenvironment facilitated enhanced endothelial cell migration, proliferation and attachment. Furthermore, in response to release of DMOG from developed hydrogel, cells showed enhanced capillary tube formation in vitro. Overall, these results demonstrate that PDA cross-linked thiol-functionalized hydrogel was developed in a facile manner under physiological conditions. These developed hydrogels could be potentially used in tissue engineering and drug delivery.

摘要

通过物理或化学方法将聚合物网络交联使用纳米粒子以获得水凝胶是一种新兴的方法。本文通过多巴胺在水-乙醇混合物中的氧化自聚合合成了聚多巴胺(PDA)纳米粒子。使用半胱胺和透明质酸(HA-Cys)通过 1-乙基-3-(3-二甲基氨基丙基)碳二亚胺- N-羟基琥珀酰亚胺(EDC-NHS)交联化学合成了巯基功能化的透明质酸。使用 PDA 纳米粒子通过迈克尔加成反应对开发的 HA-Cys 缀合物进行交联。合成的纳米粒子具有单分散性,粒径为 124 ± 8nm,具有球形形态。傅里叶变换红外光谱(FTIR)表征证实了 HA-Cys 缀合物的成功合成以及随后与 PDA 纳米粒子的交联。流变学特性研究表明,水凝胶具有可注射性,具有良好的机械稳定性。载有二甲基草酰甘氨酸(DMOG)的 PDA 纳米粒子从复合水凝胶中表现出 7 天的持续药物释放。水凝胶微环境促进内皮细胞迁移、增殖和附着。此外,在开发的水凝胶中 DMOG 释放的情况下,细胞在体外显示出增强的毛细血管形成。总之,这些结果表明,PDA 交联的巯基功能化水凝胶在生理条件下以简单的方式进行了开发。这些开发的水凝胶可能在组织工程和药物输送中得到应用。

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