Glucose-responsive polymer bearing a novel phenylborate derivative as a glucose-sensing moiety operating at physiological pH conditions
Glucose-responsive polymer bearing a novel phenylborate derivative as a glucose-sensing moiety operating at physiological pH conditions
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DOI：
10.1021/bm034139o
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发表时间：
2003-09-01
影响因子：
6.2
通讯作者：
Kataoka, K
中科院分区：
文献类型：
--
作者：
Matsumoto, A;Ikeda, S;Kataoka, K
本研究致力于开发在生理条件下（pH 7.4, 37℃）工作的新型葡萄糖反应聚合物，旨在未来用于治疗糖尿病的自我调节胰岛素输送系统。该方法包括使用新合成的苯硼酸衍生物{4-（1,6-二氧基-2,5-二氮-7-氧氨基）苯硼酸DDOPBA}作为葡萄糖感应部分，具有相当低的pK(a)（类似于7.8），以及采用聚（n -异丙基甲基丙烯酰胺）PNIPMAAm作为主链，在接近生理温度的范围内表现出临界溶液行为。在不同温度下，研究了所得共聚物的临界溶液行为的葡萄糖和ph依赖性变化，揭示了接近生理条件的葡萄糖敏感性。此外，当温度接近主链的临界溶解点时，共聚物中的dddopba片段保持恒定的表观pK(a)值，这表明苯基硼酸酯片段与聚合物主链的间距是最小化温度引起的聚合物链水化状态变化所引起的微环境效应的可行方法。
This study is devoted to the development of novel glucose-responsive polymers that operate under physiological conditions (pH 7.4, 37 degreesC), aiming for future use in a self-regulated insulin delivery system to treat diabetes mellitus. The approach involves the use of a newly synthesized phenylborate derivative {4-(1,6-dioxo-2,5-diaza-7-oxamyl) phenylboronic acid, DDOPBA} possessing an appreciably low pK(a) (similar to7.8) as a glucose-sensing moiety, as well as the adoption of poly(N-isopropylmethacrylamide), PNIPMAAm, as the main chain that exhibits critical solution behavior in the range close to physiological temperature. Glucose-and pH-dependent changes in the critical solution behavior of the resultant copolymers were investigated at varying temperatures, revealing definite glucose sensitivities near the physiological conditions. Furthermore, DDOPBA moieties in the copolymers maintained constant apparent pK(a) values even when the temperature approaches the critical solution points of the main chain, indicating that spacing of the phenylborate moiety from the polymer backbone is a feasible way to minimize the microenvironment effect caused by a temperature-induced change in the hydration state of the polymer strands.