Super long-term glycemic control in diabetic rats by glucose-sensitive LbL films constructed of supramolecular insulin assembly
Super long-term glycemic control in diabetic rats by glucose-sensitive LbL films constructed of supramolecular insulin assembly
复制标题
超分子胰岛素组装体葡萄糖敏感LbL薄膜对糖尿病大鼠的超长期血糖控制
DOI：
10.1016/j.biomaterials.2012.08.041
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发表时间：
2012-11-01
期刊：
影响因子：
14
通讯作者：
Li, Jianshu
中科院分区：
文献类型：
--
作者：
Luo, Jun;Cao, Shuqin;Li, Jianshu
在中等条件下制备猪胰岛素（P-SIA），利用硫黄素T荧光监测其超分子组装，以避免形成具有丰富β -sheet结构的成熟淀粉样原纤维。P-SIA在结构、形态和体外胰岛素持续释放能力方面具有特征。然后，以星形聚[2-（二甲氨基）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为原料，以{(star- pdmaema /P-SIA)(2) + (star- pdmaema /CAT)(1) + (star- pdmaema /GOD)(2)}(2) + star- pdmaema /GOD)(2) + star- pdmaema的形式制备葡萄糖敏感层（LbL）膜，其中CAT的加入消除了聚集的H2O2，并在较长的释放时间内维持GOD的活性。在研究范围内，单次给药可以有效控制糖尿病大鼠的血糖，长达295天无低血糖。这一惊人的结果既得益于P-SIA的固有特性，也得益于LbL膜对葡萄糖敏感的调节能力，其机制在体外和体内都得到了深入的研究。这些发现对将胰岛素超分子组装与各种功能药物递送系统、生化添加剂、生物材料和生物医学设备结合用于糖尿病治疗具有重要的启发意义。(C) 2012 Elsevier Ltd.版权所有。
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 beta-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 H2O2 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. (C) 2012 Elsevier Ltd. All rights reserved.