Development of self-regulated insulin delivery system based on novel glucose-responsive gel

基于新型葡萄糖反应凝胶的自我调节胰岛素输送系统的开发

基本信息

批准号：
10559019
负责人：
KATAOKA Kazunori
金额：
$ 7.36万
依托单位：
The University of Tokyo
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 2000
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-10559019/
关键词：
Glucose Insulin Polymeric gel Phenylboronic acid Poly (N-isopropylacrylamide)Drug delivery Diabetes Intelligent gel

项目摘要

Recently, polymeric gels which change their physicochemical properties with external stimuli have been the subject of great interest because of their potential utility as chemical valve system for controlled drug release, analytical and preparative separations, and sensor technologies. Indeed, remarkable progress has been made in the development of gels responding to physical stimuli such as heat and light. Yet, few examples are known of totally synthetic gels responding to chemical stimuli, i.e., a concentration change in particular molecules in the milieu, regardless of their wide applicability as described above. More specifically, development of sugar-responsive gels may give a great impetus to construct a self-regulating insulin-delivery system, mimicking the function of β-cells in pancreas, for the treatment of diabetes. In this research project, totally synthetic polymer gels responding to external glucose concentration was firstly prepared. The gel was composed of polymer strands showing lower critical solution temperature, such as poly (N-isopropylacrylamide) (PNIPAAm), with a small quantity of phenylboronic acid as glucose-sensing moieties. Repeated volume phase transition of the gel was demonstrated under microscopy equipped with a video monitor at isothermal condition with a change in glucose concentration due to the shift in the equilibrium of phenylboronic acid between the undissociated (or uncharged) and the dissociated (or charged) form through complexation with glucose. Further, on-off regulation of insulin release from the gel was achieved responding to a change in external glucose concentration, indicating a potential utility of this novel type of glyco-sensitive gel in self-regulated insulin delivery systems.

最近，由于其潜在的效用是用于受控药物释放，分析和准备好的分离和传感器技术的化学阀系统，因此可以通过外部刺激改变其物理性能的聚合凝胶引起了人们的关注。实际上，在凝胶响应物理刺激（例如热和光线）的凝胶发展方面取得了显着进步。然而，很少有人知道完全合成的凝胶对化学刺激响应，即，无论其较广泛的可施加性，如上所述，在环境中特定分子的浓度变化。更具体地说，糖响应性凝胶的发育可能会带来巨大的动力来构建自我调节的胰岛素传递系统，从而模仿胰腺中β细胞的功能，用于治疗糖尿病。在该研究项目中，首先制备了完全合成的聚合物凝胶对外部葡萄糖浓度的反应。凝胶由聚合物链组成，显示较低的临界溶液温度，例如聚（N-异丙基丙烯酰胺）（PNIPAAM），少量的苯基硼酸作为葡萄糖感应部分。在配备视频监测器的显微镜下，在等热条件下表明了凝胶的重复体积相变，由于苯基硼酸在未分离的（或无带电）和分离的（或带电的）形式之间通过与葡萄糖的络合形式发生了相当于苯基硼酸的变化，葡萄糖浓度的变化。此外，从凝胶中释放胰岛素释放的开关调节，以应对外部葡萄糖浓度的变化，表明这种新型类型的Glyco敏感凝胶在自调节的胰岛素递送系统中具有潜在的效用。