Glucose-Responsive Microgels Integrated with Enzyme Nanocapsules for Closed-Loop Insulin Delivery
Glucose-Responsive Microgels Integrated with Enzyme Nanocapsules for Closed-Loop Insulin Delivery
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DOI：
10.1021/nn401617u
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发表时间：
2013-08-01
期刊：
影响因子：
17.1
通讯作者：
Anderson, Daniel G.
中科院分区：
文献类型：
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作者：
Gu, Zhen;Dang, Tram T.;Anderson, Daniel G.
葡萄糖响应型剂量环胰岛素递送系统代表了1型糖尿病的理想治疗方法。在这项研究中，我们开发了均匀的可注射微凝胶，用于控制胰岛素的葡萄糖反应释放。采用一步电喷雾法制备单分散微凝胶(256+/-18µm)，由pH响应型壳聚糖基质、酶纳米胶囊和重组人胰岛素组成。葡萄糖专一性酶被共价包裹到纳米胶囊中，通过防止变性和免疫原性来提高酶的稳定性，并将基质扩散造成的损失降至最低。由于葡萄糖被酶转化为葡萄糖酸和壳聚糖网络的质子化，微凝胶体系在高血糖条件下膨胀。作为一个自我调节的阀门系统，微凝胶被调整为在正常血糖条件下以基础释放速率释放胰岛素，在高血糖条件下以较高速率释放胰岛素。最后，我们证明了这些带有酶纳米胶囊的微凝胶促进了胰岛素的释放，并导致1型糖尿病小鼠模型的血糖水平下降。
A glucose-responsive dosed-loop insulin delivery system represents the ideal treatment of type 1 diabetes mellitus. In this study, we develop uniform injectable microgels for controlled glucose-responsive release of insulin. Monodisperse microgels (256 +/- 18 mu m), consisting of a pH responsive chitosan matrix, enzyme nanocapsules, and, recombinant human insulin were fabricated through a one-step electrospray procedure. Glucose-specific enzymes were covalently encapsulated into the nanocapsules to Improve enzymatic stability by protecting from denaturation and immunogenicity as well as to minimize loss due to diffusion from the matrix. The microgel system swelled when subjected to hyperglycemic conditions, as a result of the enzymatic conversion of glucose into gluconic acid and protonation of the chitosan network. Acting as a self-regulating valve system, microgels were adjusted to release insulin at basal release rates under normoglycemic conditions and at higher rates under hyperglycemic conditions. Finally, we demonstrated that these microgels with enzyme nanocapsules facilitate insulin release and result in a reduction of blood glucose levels in a mouse model of type 1 diabetes.