Key Laboratory of Functional Polymer Materials and State Key Laboratory of Medicinal Chemical Biology, Institute of Polymer Chemistry, College of Chemistry, Nankai University, Tianjin 300071, China.
Département de Chimie, Université de Montréal, C.P. 6128, Succ. Centre-ville, Montreal, QC H3C 3J7, Canada.
J Mater Chem B. 2020 Oct 21;8(40):9335-9342. doi: 10.1039/d0tb01822h.
Insulin administration at mealtimes for the control of postprandial glucose is a major part of basal-bolus insulin therapy; however, painful subcutaneous (SC) injections lead to poor patient compliance. The microneedle (MN) patch, which allows painless transdermal drug delivery, is a promising substitute; however, it remains a big challenge to deliver insulin as rapidly as by SC injection. Here a novel MN patch is designed in which the MNs are coated with insulin/poly-l-glutamic acid (PGA) layer-by-layer (LBL) films at pH 3.0. This coating is pH-sensitive because the net charge of insulin turns from positive to negative when the pH increases from 3.0 to 7.4. As a result, when transferred to pH 7.4 media, e.g., when inserted into skin, the coating dissociates instantly and releases insulin rapidly. A brief epidermal application (<1 min) of the coated MNs is enough for complete film dissociation. More importantly, the coated MN patch exhibits a pharmacokinetic and a pharmacodynamic profile comparable to that of insulin administrated by SC injection, suggesting the coated MN patch can deliver insulin as rapidly as the SC injection. In addition, the patch exhibits excellent biocompatibility and storage stability. The new MN patch is expected to become a painless, convenient method for the control of postprandial glucose.
在进餐时进行胰岛素注射以控制餐后血糖是基础-餐时胰岛素治疗的主要部分；然而，皮下（SC）注射带来的疼痛会导致患者顺应性差。微针（MN）贴片可以实现无痛透皮药物递送，是一种很有前途的替代品；然而，要像 SC 注射那样快速地递送胰岛素仍然是一个巨大的挑战。在这里设计了一种新型 MN 贴片，其中 MN 被胰岛素/聚-L-谷氨酸（PGA）层层（LBL）薄膜在 pH 3.0 下涂覆。这种涂层具有 pH 敏感性，因为当 pH 值从 3.0 增加到 7.4 时，胰岛素的净电荷从正变为负。因此，当转移到 pH 7.4 的介质中时，例如，当插入皮肤时，涂层会立即解离并迅速释放胰岛素。经皮应用（<1 分钟）涂覆的 MN 足以实现完全的薄膜解离。更重要的是，涂覆的 MN 贴片表现出与 SC 注射给药相当的药代动力学和药效学特征，表明涂覆的 MN 贴片可以像 SC 注射一样快速递送胰岛素。此外，该贴片具有出色的生物相容性和存储稳定性。这种新型 MN 贴片有望成为一种无痛、便捷的餐后血糖控制方法。
