Water-soluble antioxidant derivative poly(triethylene glycol methyl acrylate-co-α-tocopheryl acrylate) as a potential prodrug to enable localized neuroprotection
Water-soluble antioxidant derivative poly(triethylene glycol methyl acrylate-co-α-tocopheryl acrylate) as a potential prodrug to enable localized neuroprotection
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DOI：
10.1016/j.actbio.2012.08.037
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发表时间：
2013-01-01
影响因子：
9.7
通讯作者：
He, W.
中科院分区：
文献类型：
--
作者：
Cao, Y.;He, W.
植入式微电极阵列（MEA）为有感觉或运动缺陷的个体带来了巨大的希望。然而，MEA 的长期功能仍然是一个关键障碍。本研究的目的是合成一种抗氧化剂前药，可以将其递送至植入物周围的神经组织，并提供药理库来对抗 MEA 周围的有害氧化应激。该报告以三甘醇甲酯丙烯酸酯和α-生育酚丙烯酸酯（抗氧化剂α-生育酚（维生素E，Ve）的合成衍生物）为单体进行共聚，得到不同组成的聚（三乙二醇丙烯酸甲酯-共-α-生育酚丙烯酸酯）（PVT）。与Ve较差的水溶性相反，通过调节共聚物组成，PVT前药在水中的溶解度可以高达3.1mg ml(-1)（相当于500μM Ve）。为了证明前药在 MEA 植入物中的适用性，使用氢键介导的逐层技术成功地将 PVT 沉积在聚丙烯酸 (PAA) 或单宁酸 (TA) 的硅基底上。椭圆光度法和石英晶体微天平数据表明PAA/PVT多层在生理pH下是可破坏的。相比之下，TA/PVT 多层膜是稳定的。 PVT 前药对 A172 人星形胶质细胞无细胞毒性。此外，PVT 能够在体外保护星形胶质细胞免受 H2O2 产生的氧化应激。使用自由基清除测定，保护机制归因于不稳定酯键的水解和活性 Ve 的释放。 (C) 2012 Acta Materialia Inc. 由 Elsevier Ltd 出版。保留所有权利。
Implantable microelectrode arrays (MEA) hold enormous hope for individuals with sensory or motor deficits. However, long-term function of MEA remains a critical hurdle. The objective of this study was to synthesize an antioxidant prodrug that can be delivered to the neural tissue around the implant and present a pharmacological depot to combat the injurious oxidative stress around the MEA. In this report, monomers of triethylene glycol methyl acrylate and alpha-tocopheryl acrylate, a synthetic derivative of the antioxidant alpha-tocopherol (vitamin E, Ve), were copolymerized to obtain poly(triethylene glycol methyl acrylate-co-alpha-tocopheryl acrylate) (PVT) with different compositions. In contrast to the poor water solubility of Ve, solubility of the PVT prodrug in water can reach as high as 3.1 mg ml(-1) (equivalent to 500 mu M Ve) by tuning the copolymer composition. To demonstrate the applicability of the prodrug for MEA implants, PVT was successfully deposited on silicon substrates with poly(acrylic acid) (PAA) or tannic acid (TA) using the layer-by-layer technique mediated by hydrogen bonding. Ellipsometry and quartz crystal microbalance data showed that the multilayers of PAA/PVT were destructible at physiological pH. In contrast, multilayers of TA/PVT were stable. The PVT prodrug was non-cytotoxic toward A172 human astrocytes. Furthermore, PVT was able to protect astrocytes against oxidative stress exerted by H2O2 in vitro. Using a free radical scavenging assay, the protection mechanism was attributed to the hydrolysis of the labile ester linkage and release of the active Ve. (C) 2012 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.