Synthetic "smart gel" provides glucose-responsive insulin delivery in diabetic mice.
Synthetic "smart gel" provides glucose-responsive insulin delivery in diabetic mice.
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DOI：
10.1126/sciadv.aaq0723
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发表时间：
2017-11
期刊：
影响因子：
13.6
通讯作者：
Suganami T
中科院分区：
文献类型：
--
作者：
Matsumoto A;Tanaka M;Matsumoto H;Ochi K;Moro-Oka Y;Kuwata H;Yamada H;Shirakawa I;Miyazawa T;Ishii H;Kataoka K;Ogawa Y;Miyahara Y;Suganami T
一种基于合成聚合物凝胶的胰岛素输送装置在健康和糖尿病小鼠中提供了人工胰腺样功能。虽然以前的研究已经尝试使用葡萄糖氧化酶和糖结合凝集素作为葡萄糖传感机制来创建“无电子”胰岛素递送系统，但是迄今为止还没有成功的临床转化。这些基于蛋白质的材料由于其变性和/或细胞毒性特性而不耐受长期使用和储存。我们通过设计一种不含蛋白质和完全基于合成材料的方法来提供解决方案。利用硼酸的糖响应特性，我们已经建立了一种限制在单个导管内的基于合成聚合物凝胶的胰岛素递送装置，其在体内表现出人工胰腺样功能。将该装置皮下植入健康和糖尿病小鼠体内，建立了一个由“连续葡萄糖传感”和“皮肤层”调节的胰岛素释放组成的闭环系统。结果，在胰岛素缺乏和胰岛素抵抗条件下，葡萄糖代谢响应于间质葡萄糖波动而得到控制，具有至少3周的持久性。我们的“智能凝胶”技术可以提供一个用户友好的和非常经济的（一次性）替代目前的最先进的，从而促进有效的胰岛素治疗的可用性，不仅在发展中国家的糖尿病患者，而且对那些患者，否则可能没有强烈的动机，如老年人，婴儿和需要护理的患者。
A synthetic polymer gel–based insulin delivery device provides an artificial pancreas–like function in healthy and diabetic mice. Although previous studies have attempted to create “electronics-free” insulin delivery systems using glucose oxidase and sugar-binding lectins as a glucose-sensing mechanism, no successful clinical translation has hitherto been made. These protein-based materials are intolerant of long-term use and storage because of their denaturing and/or cytotoxic properties. We provide a solution by designing a protein-free and totally synthetic material–based approach. Capitalizing on the sugar-responsive properties of boronic acid, we have established a synthetic polymer gel–based insulin delivery device confined within a single catheter, which exhibits an artificial pancreas–like function in vivo. Subcutaneous implantation of the device in healthy and diabetic mice establishes a closed-loop system composed of “continuous glucose sensing” and “skin layer”–regulated insulin release. As a result, glucose metabolism was controlled in response to interstitial glucose fluctuation under both insulin-deficient and insulin-resistant conditions with at least 3-week durability. Our “smart gel” technology could offer a user-friendly and remarkably economic (disposable) alternative to the current state of the art, thereby facilitating availability of effective insulin treatment not only to diabetic patients in developing countries but also to those patients who otherwise may not be strongly motivated, such as the elderly, infants, and patients in need of nursing care.
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影响因子：
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