More lipophilic dialkyldiamine-based diazeniumdiolates: Synthesis, characterization, and application in preparing thromboresistant nitric oxide release polymeric coatings
More lipophilic dialkyldiamine-based diazeniumdiolates: Synthesis, characterization, and application in preparing thromboresistant nitric oxide release polymeric coatings
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DOI：
10.1021/jm030286t
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发表时间：
2003-11-20
影响因子：
7.3
通讯作者：
Meyerhoff, ME
中科院分区：
文献类型：
--
作者：
Batchelor, MM;Reoma, SL;Meyerhoff, ME
介绍了一系列亲脂性二烷基二胺基二醇二氮烯鎓盐的合成、表征及其在制备抗血栓聚合物涂层中的生物医学应用。通过相应的二胺与NO的反应制备RN[N（O）NO]（-）-（CH 2）（6）（NH 2 R）-R-除以的形式的二烷基六亚甲基二胺二醇二氮烯鎓盐，其中R = CH 3、CH 2CH 3、（CH 2）（2）CH 3、（CH 2）（3）CH 3、（CH 2）（4）CH 3、（CH 2）（5）CH 3和（CH 2）（11）CH 3。R =（CH 2）（3）CH 3]可以被引入到疏水性聚合物膜（例如，增塑的PVC），并且所得材料在暴露于PBS缓冲液时长时间释放NO。从这些薄膜中释放NO的机制进行了详细研究。通过加入亲脂性阴离子物质（例如，四苯基硼酸盐衍生物）添加到聚合物材料中以缓冲有机相中质子的活性。它表明，这些新的亲脂性NO-供体在聚合物中的使用提供了定制NO释放速率的各种医疗应用的能力。作为一个例子，掺杂有N，N '-二丁基六亚甲基二胺二醇二氮烯鎓和四苯基硼酸盐衍生物的聚合物被用作绵羊血管移植物的涂层。NO释放移植物表现出增强的性能，平均95%的无血栓表面积相比，42%的相应的对照移植物植入后21天进行检查。
The synthesis, characterization, and biomedical application in preparing more thromboresistant polymeric coatings for a series of lipophilic dialkyldiamine-based diazeniumdiolates are described. Dialkylhexamethylenediamine diazeniumdiolates of the form RN[N(O)NO](-)-(CH2)(6)(NH2R)-R-divided by, where R = CH3, CH2CH3, (CH2)(2)CH3, (CH2)(3)CH3, (CH2)(4)CH3, (CH2)(5)CH3, and (CH2)(11)CH3, are prepared via reaction of the corresponding diamine with NO. The more lipophilic diazeniumdiolates [e.g., R = (CH2)(3)CH3] can be incorporated into hydrophobic polymeric films (e.g., plasticized PVC), and the resulting materials release NO for extended periods of time upon exposure to PBS buffer. The mechanism of NO release from these films is examined in detail. More stable initial NO release can be achieved by adding lipophilic anionic species (e.g., tetraphenylborate derivative) to the polymeric material to buffer the activity of protons within the organic phase. It is shown that the use of these new lipophilic NO-donors in polymers provides the ability to tailor NO release rates for a variety of medical applications. As an example, polymers doped with N,N'-dibutylhexamethylenediamine diazeniumdiolate and a tetraphenylborate derivative are employed as coatings for vascular grafts in sheep. The NO release grafts exhibited enhanced performance and had an average 95% thrombus-free surface area compared to 42% for the corresponding control grafts when examined after 21d of implantation.