A depot-forming glucagon-like peptide-1 fusion protein reduces blood glucose for five days with a single injection.
A depot-forming glucagon-like peptide-1 fusion protein reduces blood glucose for five days with a single injection.
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DOI：
10.1016/j.jconrel.2013.07.021
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发表时间：
2013-11-28
期刊：
影响因子：
--
通讯作者：
Chilkoti A
中科院分区：
文献类型：
--
作者：
Amiram M;Luginbuhl KM;Li X;Feinglos MN;Chilkoti A
多肽药物是一类令人兴奋的药物，用于治疗各种疾病；然而，它们的半衰期很短，需要多次和频繁注射，从而产生不良的副作用。在这里，我们描述了一种新的肽递送系统，旨在结合延长循环时间和延长释放制剂的有吸引力的特征。该系统由胰高血糖素样肽-1组成，胰高血糖素样肽-1是一种2型糖尿病药物，与热反应性弹性蛋白样多肽（ELP）融合，ELP在室温和体温之间经历可溶-不溶相变，从而形成可注射储库。我们合成了一组GLP-1-ELP融合物，并在体外验证了它们的蛋白水解稳定性和效力。值得注意的是，单次注射库型GLP-1-ELP融合物可以降低小鼠的血糖水平长达5天，比注射天然肽的时间长120倍。这些发现证明了利用elp从仓库释放肽- elp融合物的独特优势，并结合增强的体循环来创建可调节的肽递送系统。
Peptide drugs are an exciting class of pharmaceuticals for the treatment of a variety of diseases; however, their short half-life dictates multiple and frequent injections causing undesirable side-effects. Herein, we describe a novel peptide delivery system that seeks to combine the attractive features of prolonged circulation time with a prolonged release formulation. This system consists of glucagon-like peptide-1, a type-2 diabetes drug fused to a thermally responsive, elastin-like-polypeptide (ELP) that undergoes a soluble-insoluble phase transition between room temperature and body temperature, thereby forming an injectable depot. We synthesized a set of GLP-1-ELP fusions and verified their proteolytic stability and potency in vitro. Significantly, a single injection of depot forming GLP-1-ELP fusions reduced blood glucose levels in mice for up to 5 days, 120 times longer than an injection of the native peptide. These findings demonstrate the unique advantages of using ELPs to release peptide-ELP fusions from a depot combined with enhanced systemic circulation to create a tunable peptide delivery system.
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影响因子：
14.8
作者：
Greenfield, Norma J.
通讯作者：
Greenfield, Norma J.
DOI：
10.1073/pnas.1214518110
发表时间：
2013-02-19
影响因子：
11.1
作者：
Amiram, Miriam;Luginbuhl, Kelli M.;Chilkoti, Ashutosh
通讯作者：
Chilkoti, Ashutosh
影响因子：
8
作者：
Christensen, Trine;Amiram, Miriam;Chilkoti, Ashutosh
通讯作者：
Chilkoti, Ashutosh
影响因子：
--
作者：
HUPESODMANN, K;MCGREGOR, GP;VOIGT, K
通讯作者：
VOIGT, K
影响因子：
5.8
作者：
Madsbad, S.;Kielgast, U.;Holst, J. J.
通讯作者：
Holst, J. J.