Glucose-responsive polymer gel bearing phenylborate derivative as a glucose-sensing moiety operating at the physiological pH
Glucose-responsive polymer gel bearing phenylborate derivative as a glucose-sensing moiety operating at the physiological pH
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DOI：
10.1021/bm0345413
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发表时间：
2004-05-01
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;Yoshida, R;Kataoka, K
这项工作试图制备一种完全合成的，葡萄糖响应性的聚合物凝胶轴承苯硼酸酯衍生物作为传感器部分的葡萄糖，为未来使用的自我调节的胰岛素输送系统。使系统在生理条件下运行的分子策略（pH7.4，37 ℃），其涉及使用新型苯基硼酸酯衍生物{4-（1，6-二氧代-2，5-二氮杂-7-草戊基）苯基硼酸：DDOPBA}具有相当低的pK（α）（类似于7.8），采用聚乙烯（N异丙基甲基丙烯酰胺）（PNIPMAAm）的主链，其本身经历了急剧的热诱导相变在其LCST约40 ℃，以及引入甲基丙烯酸的羧基作为第三共聚单体。基于在存在和不存在葡萄糖的情况下测定的平衡溶胀度的变化，对于各种pH和温度条件，评价所获得的凝胶的葡萄糖响应行为。作为组合分子效应的结果，在生理pH和接近生理条件的温度范围（例如30 ℃）内实现了系统的足够灵敏度。此外，在这些条件下，葡萄糖诱导的凝胶的连续体积变化被证明，这发生在一个显着的浓度依赖性的方式。在这些实验中，观察了在正常血糖水平范围内诱导凝胶响应的临界葡萄糖浓度。这些观察结果可能为我们提供了一个极好的前景，使用凝胶作为一个自我调节，胰岛素输送系统离散切换释放在正常的。
The work attempts to prepare a totally synthetic, glucose-responsive polymer gel bearing a phenylborate derivative as a sensor moiety to glucose, for future use as a self-regulated insulin delivery system. The molecular strategies to enable the system to be operated under physiological conditions (pH 7.4, 37 degreesC) are presented that involve the use of a novel pherylborate derivative {4-(1,6-dioxo-2,5-diaza-7-oxamyl) phenylboronic acid: DDOPBA} possessing an appreciably low pK(a) (similar to7.8), the adoption of poly(Nisopropylmethacrylamide) (PNIPMAAm) for the main chain, which itself undergoes a sharp thermo-induced phase transition at its LCST around 40 degreesC, as well as the introduction of a carboxyl group of methacrylic acid as the third comonomer. Glucose-responsive behaviors of the obtained gels were evaluated based on the changes in the equilibrium swelling degree determined in the presence and the absence of glucose, for various pH and temperature conditions. As a consequence of the combined molecular effects, a sufficient sensitivity of the system was accomplished at physiological pH and in the temperature range close to the physiological condition such as 30 degreesC. Furthermore, the glucose-induced continuous volume changes of the gels were demonstrated under those conditions, which occurred in a remarkably concentration-dependent manner. In these experiments, the critical glucose concentrations to induce the gels' responses in the range of normoglycemic sugar level were observed. These observations may provide us with an excellent prospect for the use of the gel as a self-regulated, insulin-delivery system discretely switching the release at the normoglycemia.