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，随着外部刺激而改变其物理化学性质的聚合物凝胶已成为人们关注的焦点，因为它们作为用于控制药物释放、分析和制备分离以及传感器技术的化学阀系统的潜在用途。然而，尽管如上所述它们具有广泛的适用性，但对化学刺激（即环境中特定分子的浓度变化）做出反应的全合成凝胶的例子却很少。更具体地说，糖响应凝胶的开发可能会极大地推动构建自我调节的胰岛素输送系统，模仿胰腺中β细胞的功能，用于治疗糖尿病。在这个研究项目中，完全合成的聚合物凝胶。首先制备了响应外部葡萄糖浓度的凝胶，其由具有较低临界溶液温度的聚合物链组成，例如聚（N-异丙基丙烯酰胺）（PNIPAAm），并含有少量的聚合物。在配备有视频监视器的显微镜下，在等温条件下证明了凝胶的重复体积相变，由于苯基硼酸在未解离（或不带电）之间的平衡的变化，导致葡萄糖浓度发生变化。此外，响应外部葡萄糖浓度的变化实现了凝胶中胰岛素释放的开关调节，这表明了潜在的效用。这种新型糖敏感凝胶在自我调节胰岛素输送系统中的应用。