Enzymatically degradable nitric oxide releasing S-nitrosated dextran thiomers for biomedical applications
Enzymatically degradable nitric oxide releasing S-nitrosated dextran thiomers for biomedical applications
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DOI：
10.1039/c2jm34834a
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发表时间：
2012-11-21
影响因子：
--
通讯作者：
Reynolds，Melissa M.
中科院分区：
文献类型：
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作者：
Damodaran，Vinod B.;Place，Laura W.;Reynolds，Melissa M.
在此，我们报告的发展和评价酶降解的一氧化氮（NO）释放S-亚硝化葡聚糖硫代聚物作为有效的生物医学材料。这些材料的特征在于它们在动脉血液条件下释放NO的特异性，随后是它们对通过葡聚糖酶进行酶降解的敏感性。我们用于硫醇掺入的非常特异性的缀合化学导致所得S-亚硝基硫醇部分的特征稳定化，并因此产生用于NO的储存和受控递送的稳定前药。我们使用多种独立的分析技术评估了NO负载和释放动力学的程度，并将这些与结合到葡聚糖主链上的硫醇部分相关的结构和环境相关联。最后，酶促降解动力学，其次是通过监测分子量分布，使用凝胶渗透色谱法，并使用完善的模型预测的结果进行解释。
Herein we report the development and evaluation of enzymatically degradable nitric oxide (NO) releasing S-nitrosated dextran thiomers as potent biomedical materials. These materials are characterized by their specificity to release NO under arterial blood conditions, followed by their susceptibility to undergo enzymatic degradation by dextranase. The very specific conjugation chemistries we employed for the thiol incorporation resulted in characteristic stabilization of the resulting S-nitrosothiol moieties, and consequently yielded stable pro-drugs for the storage and controlled delivery of NO. We evaluated the extent of NO loading and release kinetics using multiple and independent analytical techniques, and related these to the structure and environment associated with the thiol moiety incorporated onto the dextran backbone. Finally, the enzymatic degradation kinetics was followed by monitoring the molecular weight profile using gel permeation chromatography, and the results were interpreted using well-established model predictions.