Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University , Raleigh, North Carolina 27695, United States.
State Key Laboratory of Polymer Chemistry and Physics, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences , Jilin, 130022, People's Republic of China.
ACS Nano. 2017 Jan 24;11(1):613-620. doi: 10.1021/acsnano.6b06892. Epub 2017 Jan 4.
A self-regulated "smart" insulin administration system would be highly desirable for diabetes management. Here, a glucose-responsive insulin delivery device, which integrates HO-responsive polymeric vesicles (PVs) with a transcutaneous microneedle-array patch was prepared to achieve a fast response, excellent biocompatibility, and painless administration. The PVs are self-assembled from block copolymer incorporated with polyethylene glycol (PEG) and phenylboronic ester (PBE)-conjugated polyserine (designated mPEG-b-P(Ser-PBE)) and loaded with glucose oxidase (GOx) and insulin. The polymeric vesicles function as both moieties of the glucose sensing element (GOx) and the insulin release actuator to provide basal insulin release as well as promote insulin release in response to hyperglycemic states. In the current study, insulin release responds quickly to elevated glucose and its kinetics can be modulated by adjusting the concentration of GOx loaded into the microneedles. In vivo testing indicates that a single patch can regulate glucose levels effectively with reduced risk of hypoglycemia.
对于糖尿病管理来说，一种自我调节的“智能”胰岛素给药系统是非常理想的。在这里，我们制备了一种葡萄糖响应性胰岛素给药装置，该装置将 HO 响应性聚合物囊泡（PVs）与经皮微针阵列贴片集成在一起，以实现快速响应、优异的生物相容性和无痛给药。PVs 由嵌段共聚物自组装而成，共聚物中掺入了聚乙二醇（PEG）和苯硼酸酯（PBE）-接枝聚丝氨酸（命名为 mPEG-b-P（Ser-PBE）），并负载了葡萄糖氧化酶（GOx）和胰岛素。聚合物囊泡既作为葡萄糖传感元件（GOx）的两个部分，又作为胰岛素释放执行器，以提供基础胰岛素释放，并在高血糖状态下促进胰岛素释放。在本研究中，胰岛素释放对升高的葡萄糖迅速响应，并且其动力学可以通过调节加载到微针中的 GOx 的浓度来调节。体内测试表明，单个贴片可以有效调节血糖水平，降低低血糖风险。
