Effect of the Incorporation of Amino Groups in a Glucose-responsive Polymer Complex Having Phenylboronic Acid Moieties
Effect of the Incorporation of Amino Groups in a Glucose-responsive Polymer Complex Having Phenylboronic Acid Moieties
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DOI：
10.1002/pat.1991.220020508
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发表时间：
1991-10-01
影响因子：
3.4
通讯作者：
Sakurai, Yasuhisa
中科院分区：
文献类型：
--
作者：
Kitano, Shigeru;Hisamitsu, Issei;Sakurai, Yasuhisa
研究了一种对葡萄糖敏感的新型聚合物络合物体系作为制备化学调节型胰岛素释放体系的候选材料。采用自由基共聚法合成了N-乙烯-2-吡咯烷酮(NVP)、3-丙烯酰胺基苯基硼酸(AAM-PBA)和N，N-二甲氨基丙基丙烯酰胺(DMAPAA)三元共聚物(聚(NVP-co-PBA-co-DMAPAA))。该共聚物中的苯基硼酸基作为葡萄糖传感器部分。聚(NVP-co-PBA-co-DMAPAA)在pH值为312的范围内可溶于水，而NVP和AAm-PBA的二元共聚物(Poly(NVP-co-PBA))只能在碱性水条件下溶解，其中硼酸基是以四面体电离形式存在的。聚(NVP-co-PBA-DMAPAA)中的质子化氨基有助于提高聚合物在生理和酸性水环境中的溶解度。此外，聚(NVP-co-PBA-co-DMAPAA)在pH 7.4的磷酸盐缓冲溶液中与聚乙烯醇(PVA)形成稳定的聚合物络合物凝胶，这是由于三元共聚物中的硼酸基团与PVA中的二醇单元之间形成了共价键。在加入葡萄糖后，由于凝胶向溶胶态的转变，肌红蛋白作为模型蛋白的释放量立即增加，这表明该复合凝胶作为胰岛素葡萄糖响应型递送系统的候选材料是可行的。
A novel polymer complex system sensitive to glucose was studied as a candidate material for formulating a chemically regulated insulin release system. A ternary copolymer of N-vinyl-2-pyrrolidone (NVP), 3-acrylamidophenylboronic acid (AAm-PBA) and N,N-dimethylaminopropylacrylamide (DMAPAA) (poly(NVP-co-PBA-co-DMAPAA)) was synthesized by radical copolymerization. The phenylboronic acid group in this copolymer serves as a glucose sensor moiety. Poly(NVP-co-PBA-co-DMAPAA) was soluble in water in the pH range of 312, in sharp contrast to a binary copolymer of NVP and AAm-PBA (poly(NVP-co-PBA)) which showed solubility only under alkaline aqueous conditions, where the boronic acid group is in a tetrahedral ionized form. The protonated amino group in poly(NVP-co-PBA-DMAPAA) contributed to increase the solubility of the polymer under physiological and acidic aqueous conditions. Furthermore, poly(NVP-co-PBA-co-DMAPAA) formed a stable polymer complex gel with poly(vinyl alcohol) (PVA) in pH 7.4 phosphate buffered solution due to the formation of a covalent linkage between the boronic acid groups in ternary copolymer and diol units in PVA. The release of myoglobin as model protein from the complex gel was increased immediately after the addition of glucose, due to the transition of gel into sol state, indicating the feasibility of this complex gel as a candidate material for a glucose-responsive delivery system for insulin.