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首页> 外文期刊>ACS applied materials & interfaces >Sustained Release Strategy Designed for Lixisenatide Delivery to Synchronously Treat Diabetes and Associated Complications
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Sustained Release Strategy Designed for Lixisenatide Delivery to Synchronously Treat Diabetes and Associated Complications

机译：持续释放策略，专为LixIsenatide交付而同步治疗糖尿病和相关并发症

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Diabetes and its complications have become a global challenge of public health. Herein, we aimed to develop a long-acting delivery system of lixisenatide (Lixi), a glucose-dependent antidiabetic peptide, based on an injectable hydrogel for the synchronous treatment of type 2 diabetes mellitus (T2DM) and associated complications. Two triblock copolymers, poly(epsilon-caprolactone-co-glycolic acid)-poly(ethylene glycol)-poly(epsilon-caprolactone-co-glycolic acid) and poly(D,L-lactic acid-co-glycolic acid)-poly(ethylene glycol)-poly(D,L-lactic acid-co-glycolic acid) possessing temperature-induced sol-gel transitions, were synthesized by us. Compared to the two single-component hydrogels, their 1/1 mixture hydrogel not only maintained the temperature-induced gelation but also exhibited a steadier degradation profile in vivo. Both in vitro and in vivo release studies demonstrated that the mixture hydrogel provided the sustained release of Lixi for up to 9 days, which was attributed to balanced electrostatic interactions between the positive charges in the peptide and the negative charges in the polymer carrier. The hypoglycemic efficacy of Lixi delivered from the mixture hydrogel after a single subcutaneous injection into diabetic db/db mice was comparable to that of twice-daily administrations of Lixi solution for up to 9 days. Furthermore, three successive administrations of the abovementioned gel system within a month significantly increased the plasma insulin level, lowered glycosylated hemoglobin, and improved the pancreatic function of the animals. These results were superior or equivalent to those of twice-daily injections of Lixi solution for 30 days, but the number of injections was markedly reduced from 60 to 3. Finally, an improvement in hyperlipidemia, augmentation of nerve fiber density, and enhancement of motor nerve conduction velocity in the gel formulation-treated db/db mice indicated that the sustained delivery of Lixi arrested and even ameliorated diabetic complications. These findings suggested that the Lixi-loaded mixture hydrogel has great potential for the treatment of T2DM with significant improvements in the health and quality of life of patients.
机译：糖尿病及其并发症已成为公共卫生的全球挑战。在此，我们旨在开发Lixisenatide（Lixi）的长效输送系统，葡萄糖依赖性抗糖尿病肽，基于可注射水凝胶，用于同步治疗2型糖尿病（T2DM）和相关并发症。两种三嵌段共聚物，聚（ε-己内酯 - 共乙醇酸） - 聚（乙二醇） - 聚（ε-己内酯 - 共乙醇酸）和聚（D，L-乳酸 - 共乙醇酸） - 聚氯乙烯（乙二醇） - 通过我们合成具有温度诱导的溶胶转变的乙二醇（D，L-乳酸 - 共乙醇酸）。与两个单组分水凝胶相比，它们的1/1混合物水凝胶不仅保持温度诱导的凝胶化，而且还在体内表现出销售的降解曲线。体外和体内释放研究既表明，混合物水凝胶提供了最多9天的Lixi持续释放，其归因于肽中的正电荷与聚合物载体中的负电荷之间的平衡静电相互作用。在单一皮下注射到糖尿病DB / dB小鼠中，丽西含量从混合物水凝胶中递送的降血糖疗效与LIXI溶液的两次溶液中最多9天相当。此外，在一个月内，在一个月内进行三次上述凝胶系统显着增加了血浆胰岛素水平，降低糖基化血红蛋白，并改善了动物的胰腺功能。这些结果是优异的或等同于丽西溶液的两次注射30天的结果，但注射次数从60〜3中显着降低。最后，高脂血症的改善，增加神经纤维密度，以及电动机的增强凝胶制剂处理的DB / DB小鼠中枢神经传导速度表明，丽西被捕的持续交付甚至改善了糖尿病并发症。这些研究结果表明，LIXI加载的混合物水凝胶具有巨大的治疗T2DM，具有显着改善患者的健康和生活质量的显着改善。

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