S-Nitrosated biodegradable polymers for biomedical applications: synthesis, characterization and impact of thiol structure on the physicochemical properties
S-Nitrosated biodegradable polymers for biomedical applications: synthesis, characterization and impact of thiol structure on the physicochemical properties
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DOI：
10.1039/c2jm16554f
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发表时间：
2012-01-01
影响因子：
--
通讯作者：
Reynolds, Melissa M.
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文献类型：
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作者：
Damodaran, Vinod B.;Joslin, Jessica M.;Reynolds, Melissa M.
通过衍生化具有独特巯基结构的聚乳酸-共羟基乙酸-共羟甲基丙酸（PLGH）聚合物，并与亚硝酸丁酯进行亚硝化反应，合成了一类新型的一氧化氮（NO）释放生物可降解聚合物。巯基化的程度取决于巯基部分本身，其掺入效率如下：半胱胺>半胱氨酸>同型半胱氨酸。谷胱甘肽和青霉胺没有明显的掺入。与悬垂硫醇相关的结构和聚合物环境与所得聚合物的物理化学性质有关。为了量化s -亚硝化的程度，化学发光和紫外可见光谱技术相结合。半胱氨酸和同型半胱氨酸衍生物的亚硝化程度最高，分别为93 +/- 3%和96 +/- 3%，半胱氨酸次之，为43 +/- 1%。基于每种亚硝化聚合物的RSNO形成的量化，热分解导致NO几乎完全回收。我们对硫醇结构、掺入程度和随后的亚硝化的控制能力对产生的NO释放动力学的最终范围至关重要。这些材料的功能用途证明了这些无毒聚合物在生理条件下释放NO，具有适合于组织支架的降解特征，并且可以制备成静电纺纳米纤维，通常用于组织和骨再生应用。
A new class of nitric oxide (NO)-releasing biodegradable polymers has been synthesized by derivatizing poly(lactic-co-glycolic-co-hydroxymethyl propionic acid) (PLGH) polymers with structurally unique thiol functionalities followed by nitrosation with t-butyl nitrite to yield pendant S-nitrosothiol moieties. The extent of thiolation was found to be dependent on the thiol moiety itself with the efficiency of incorporation as follows: cysteamine > cysteine > homocysteine. Glutathione and penicillamine were not incorporated to any significant extent. The structure and polymer environment associated with the pendant thiol has been related to the physicochemical properties of the resulting polymers. To quantify the extent of S-nitrosation, chemiluminescence and UV-visible spectroscopy techniques were employed in combination. The cysteamine and homocysteine derivatives were found to have the highest extent of nitrosation at 93 +/- 3% and 96 +/- 3%, respectively, followed by 43 +/- 1% for cysteine. Thermal decomposition led to near-complete recovery of NO based upon the quantification of the RSNO formation for each nitrosated polymer. Our ability to exert control over the thiol structure, extent of incorporation and the subsequent nitrosation is crucial to the resulting range of NO release kinetics that were yielded. The functional utility of these materials is demonstrated in that these non-toxic polymers release NO under physiological conditions, have degradation profiles that are appropriate for tissue scaffolds and can be prepared as electrospun nanofibers, commonly used in tissue and bone regeneration applications.