Simultaneously physically and chemically gelling polymer system utilizing a poly(NIPAAm-co-cysteamine)-based copolymer
Simultaneously physically and chemically gelling polymer system utilizing a poly(NIPAAm-co-cysteamine)-based copolymer
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DOI：
10.1021/bm070267r
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发表时间：
2007-07-01
影响因子：
6.2
通讯作者：
Vernon, Brent L.
中科院分区：
文献类型：
--
作者：
Robb, Stephanie A.;Lee, Bae Hoon;Vernon, Brent L.
这项工作的目的是创建一个在原位物理和化学交联的水凝胶在体内应用。采用自由基聚合法合成了N-异丙基丙烯酰胺（NIPAAm）和N-丙烯酰氧基琥珀酰亚胺（NASI）。聚（NIPAAm-co-NASI）通过半胱胺的胺基对NASI的羰基进行亲核攻击而进一步改性以获得聚（NIPAAm-co-半胱胺）。通过核磁共振证实了修饰。除了由于NIPAAm的存在而产生的温敏性物理胶凝之外，当与聚（乙二醇）二丙烯酸酯混合时，该系统还通过迈克尔型加成反应化学胶凝。物理和化学凝胶化的存在导致与纯物理凝胶相比大大改善的材料性质。共聚物的化学凝胶化时间不受存在的硫醇的量的显著影响，这是由于含有更多硫醇的共聚物的pK（a）增加。此外，共聚物的溶胀高度依赖于温度和硫醇含量。最后，迈克尔型加成反应中的亲核攻击速率被证明是高度依赖于pH值和硫醇与丙烯酸酯的摩尔比。由于机械性能的改善，这种材料可能比其他热敏物理凝胶更适合长期功能替代应用。随着进一步的开发和生物相容性测试，这种材料可能会作为一种温度响应性可注射生物材料用于功能性栓塞。
The objective of this work was to create an in situ physically and chemically cross-linking hydrogel for in vivo applications. N-Isopropylacrylamide (NIPAAm) was copolymerized with N-acryloxysuccinimide (NASI) via free radical polymerization. Poly(NIPAAm-co-NASI) was further modified to obtain poly(NIPAAm-co-cysteamine) through a nucleophilic attack on the carbonyl group of the NASI by the amine group of the cysteamine. Modification was verified by nuclear magnetic resonance. In addition to thermoresponsive physical gelling due to the presence of NIPAAm, this system also chemically gels via a Michael-type addition reaction when mixed with poly(ethylene glycol) diacrylate. The presence of both physical and chemical gelation resulted in material properties that are much improved compared to purely physical gels. The chemical gelation time of the copolymers was not significantly affected by the amount of thiol present due to the increased pK(a) of the copolymer containing more thiols. In addition, the swelling of the copolymers was highly dependent on the temperature and thiol content. Last, the rate of nucleophilic attack in the Michael-type addition reaction was shown to be highly dependent on pH and on the mole ratio of thiol to acrylate. Due to the improved mechanical properties, this material may be better suited for long-term functional replacement applications than other thermosensitive physical gels. With further development and biocompatibility testing, this material could potentially be applied as a temperature-responsive injectable biomaterial for functional embolization.