In vivo variable and multi-day response from an insulin-releasing photoactivated depot.
In vivo variable and multi-day response from an insulin-releasing photoactivated depot.
复制标题
体内胰岛素释放光激活库的可变和多天反应。
DOI：
10.1016/j.bmcl.2023.129388
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发表时间：
2023
影响因子：
2.7
通讯作者：
Friedman,SimonH
中科院分区：
文献类型：
--
作者：
Nadendla,Karthik;Chintala,Swetha;Kover,Karen;Friedman,SimonH
以前我们已经证明，光可以用来控制糖尿病动物的胰岛素释放，然后降低血糖。这是使用注射到皮肤中的胰岛素的光活化贮库（PAD）并由小型外部LED光源照射来实现的。在这项工作中，我们第一次证明了剂量反应，表明我们可以通过改变给予的光量来改变胰岛素释放和相应的血糖降低。除了证明剂量反应外，我们还显示了多日贮库反应，胰岛素在两个不同的日子从同一贮库中释放。这些研究中使用的材料是CD-胰岛素，这是一种连接有高度非极性环十二烷基基团的胰岛素形式，显著降低了改性材料的溶解度，并使其在注射时形成储库。在光解时，环十二烷基基团被去除，释放出完全天然的可溶性胰岛素。所证明的可变响应和多日响应强烈支持PAD方法用于治疗肽的可变和延长释放的潜在效用。
Previously we have demonstrated that light can be used to control the release of insulin in diabetic animals, followed by a reduction in blood glucose. This is accomplished using a photoactivated depot (PAD) of insulin injected into the skin, and irradiated by a small external LED light source. In this work for the first time we demonstrate dose–response, showing that we can vary insulin release and commensurate blood glucose reduction by varying the amount of light administered. In addition to demonstrating dose–response, we have shown multi-day depot response, with insulin being released on two different days from the same depot. The material used in these studies was CD-insulin, a form of insulin that has a highly non-polar cyclododecyl group attached, markedly reducing the solubility of the modified material, and allowing it to form a depot upon injection. Upon photolysis, the cyclododecyl group is removed, releasing fully native, soluble insulin. Variable response and multi-day response as demonstrated strongly support the potential utility of the PAD approach for the variable and extended release of therapeutic peptides.