Takei Chihiro, Ohno Yui, Seki Tomohiro, Miki Ryotaro, Seki Toshinobu, Egawa Yuya
Faculty of Pharmacy and Pharmaceutical Sciences, Josai University.
Chem Pharm Bull (Tokyo). 2018;66(4):368-374. doi: 10.1248/cpb.c17-00817.
Previous studies have shown that reversible chemical bond formation between phenylboronic acid (PBA) and 1,3-diol can be utilized as the driving force for the preparation of layer-by-layer (LbL) films. The LbL films composed of a PBA-appended polymer and poly(vinyl alcohol) (PVA) disintegrated in the presence of sugar. This type of LbL films has been recognized as a promising approach for sugar-responsive drug release systems, but an issue preventing the practical application of LbL films is combining them with insulin. In this report, we have proposed a solution for this issue by using PBA-appended insulin as a component of the LbL film. We prepared two kinds of PBA-appended insulin derivatives and confirmed that they retained their hypoglycemic activity. The LbL films composed of PBA-appended insulin and PVA were successfully prepared through reversible chemical bond formation between the boronic acid moiety and the 1,3-diol of PVA. The LbL film disintegrated upon treatment with sugars. Based on the results presented herein, we discuss the suitability of the PBA moiety with respect to hypoglycemic activity, binding ability, and selectivity for D-glucose.
先前的研究表明，苯基硼酸（PBA）与1,3 - 二醇之间可逆的化学键形成可被用作制备层层（LbL）膜的驱动力。由连接有PBA的聚合物和聚乙烯醇（PVA）组成的LbL膜在糖存在的情况下会分解。这种类型的LbL膜已被认为是用于糖响应性药物释放系统的一种有前景的方法，但阻碍LbL膜实际应用的一个问题是将它们与胰岛素结合。在本报告中，我们通过使用连接有PBA的胰岛素作为LbL膜的一个组分，为这个问题提出了一种解决方案。我们制备了两种连接有PBA的胰岛素衍生物，并证实它们保留了降血糖活性。通过硼酸部分与PVA的1,3 - 二醇之间可逆的化学键形成，成功制备了由连接有PBA的胰岛素和PVA组成的LbL膜。该LbL膜在糖处理后会分解。基于本文给出的结果，我们讨论了PBA部分在降血糖活性、结合能力和对D - 葡萄糖的选择性方面的适用性。
