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Super long-term glycemic control in diabetic rats by glucose-sensitive LbL films constructed of supramolecular insulin assembly

机译:超分子胰岛素组装体构建的葡萄糖敏感性LbL膜对糖尿病大鼠的超长期血糖控制

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The supramolecular assembly of porcine insulin (P-SIA) is prepared at moderate condition and monitored by Thioflavin T fluorescence to avoid the formation of mature amyloid fibrils with β-sheet rich structure. P-SIA is characterized in terms of structure, morphology and the capability of sustained insulin release in vitro. Then, a glucose-sensitive layer-by-layer (LbL) film is fabricated with star poly[2-(dimethylamino)ethyl methacrylate] (star-PDMAEMA), glucose oxidase (GOD), catalase (CAT) and P-SIA in the form of {(Star-PDMAEMA/P-SIA) 2 + (Star-PDMAEMA/CAT) 1 + (Star-PDMAEMA/GOD) 2} 2 + Star-PDMAEMA, in which the CAT is introduced to eliminate the aggregated H 2O 2 and maintain the activity of GOD in the long release time. Within the scope of the investigation, a single dose administration could provide effective glycemic control in diabetic rats for up to 295 days without hypoglycemia. The striking result is contributed both by the inherent property of P-SIA and the glucose-sensitive regulation capability of the LbL film, for which the mechanism was thoroughly investigated both in vitro and in vivo. These findings are valuable to inspire more researches to combine supramolecular insulin assembly with various functional drug delivery systems, biochemical additives, biomaterials and biomedical devices for diabetic therapy.
机译:猪胰岛素(P-SIA)的超分子组装是在中等条件下制备的,并通过硫黄素T荧光进行监测,以避免形成富含β-折叠结构的成熟淀粉样蛋白原纤维。 P-SIA的特征在于结构,形态和体外胰岛素持续释放的能力。然后,用星形聚[2-(二甲基氨基)甲基丙烯酸乙酯](star-PDMAEMA),葡萄糖氧化酶(GOD),过氧化氢酶(CAT)和P-SIA制备葡萄糖敏感的逐层(LbL)膜。 {(Star-PDMAEMA / P-SIA)2 +(Star-PDMAEMA / CAT)1 +(Star-PDMAEMA / GOD)2} 2 + Star-PDMAEMA的形式,其中引入了CAT以消除聚集的H 2O 2并在较长的释放时间内保持了GOD的活性。在研究范围内,单剂量给药可以在糖尿病大鼠中提供长达295天的有效血糖控制而无低血糖。 P-SIA的固有性质和LbL膜对葡萄糖的敏感调节能力都对这一惊人的结果做出了贡献,为此,在体内和体外对这种机理进行了彻底的研究。这些发现对于激发更多的研究以将超分子胰岛素组装体与各种功能性药物输送系统,生化添加剂,生物材料以及用于糖尿病治疗的生物医学装置相结合具有宝贵的价值。

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