Beijing Laboratory of Biomedical Materials, College of Materials Science and Engineering, Beijing University of Chemical Technology, Beijing 100029, PR China.
Beijing Laboratory of Biomedical Materials, College of Materials Science and Engineering, Beijing University of Chemical Technology, Beijing 100029, PR China.
Adv Drug Deliv Rev. 2018 Mar 1;127:119-137. doi: 10.1016/j.addr.2018.03.011. Epub 2018 Mar 29.
Diabetes, a metabolic disorder of glucose, is a serious chronic disease and an important public health problem. Insulin is one of the hormones for modulating blood glucose level and the products of which is indispensable for most diabetes patients. Introducing microneedles (MNs) to insulin delivery is promising to pave the way for modulating glucose level noninvasively of diabetes patients, as which born to be painless, easy to handle and no need of any power supply. In this work, we review the process of insulin delivery systems (IDSs) based on MN technology in terms of two categories: drug free MNs and drug loaded MNs. Drug free MNs include solid MNs ("poke and patch"), hollow MNs ("poke and flow") and reservoir-based swelling MNs ("poke and swell R-type"), and drug loaded MNs include coated MNs ("coat and poke"), dissolving MNs ("poke and release") and insulin incorporated swelling MNs ("poke and swell I-type"). Majority researches of MN-based IDSs have been conducted by using hollow MNs or dissolving MNs, and almost all clinical trials for MN-based IDSs have employed hollow MNs. "Poke and patch" approach dramatically increase skin permeability compared to traditional transdermal patch, but MNs fabricated from silicon or metal may leave sharp waste in the skin and cause a safety issue. "Poke and flow" approach, similar to transitional subcutaneous (SC) injection, is capable of producing faster insulin absorption and action than SC injection but may associate with blockage, leakage and low flow rate. Coated MNs are able of retaining the activity of drug, which loaded in a solid phase, for a long time, however have been relatively less studied for insulin application as the low drug dosing. "Poke and release" approach leaves no biohazardous sharp medical waste and is capable of rapid drug release. "Poke and swell R-type" can be seen as a combination of "poke and flow" and "poke and patch" approach, while "poke and swell I-type" is an approach between "coat and poke" and "poke and release" approach. Insulin MNs are promising for painless diabetes therapeutics, and additional efforts for addressing fundamental issues including the drug loading, the PK/PD profile, the storage and the safety of insulin MNs will accelerate the clinical transformation.
糖尿病是一种葡萄糖代谢紊乱的代谢性疾病，是一种严重的慢性疾病，也是一个重要的公共卫生问题。胰岛素是调节血糖水平的激素之一，对于大多数糖尿病患者来说，胰岛素是不可或缺的。将微针（MNs）引入胰岛素给药系统具有很大的前景，可以为糖尿病患者非侵入性地调节血糖铺平道路，因为它生来就是无痛、易于操作且不需要任何电源。在这项工作中，我们根据两类微针技术的胰岛素给药系统（IDSs）：无药物微针和载药微针，对其进行了综述。无药物微针包括实心微针（“戳刺和贴片”）、空心微针（“戳刺和流动”）和基于储库的溶胀微针（“戳刺和溶胀 R 型”），载药微针包括涂层微针（“包衣和戳刺”）、溶解微针（“戳刺和释放”）和胰岛素结合溶胀微针（“戳刺和溶胀 I 型”）。基于 MN 的 IDSs 的大多数研究都使用空心 MN 或溶解 MN 进行，并且几乎所有基于 MN 的 IDSs 的临床试验都使用空心 MN。“戳刺和贴片”方法与传统的透皮贴剂相比，显著增加了皮肤通透性，但由硅或金属制成的 MN 可能会在皮肤中留下锐利的废物，引起安全问题。“戳刺和流动”方法类似于过渡性皮下（SC）注射，能够产生比 SC 注射更快的胰岛素吸收和作用，但可能与阻塞、泄漏和低流速有关。涂层 MN 能够长时间保持药物的活性，而药物负载在固体相中，然而，由于药物剂量低，用于胰岛素应用的研究相对较少。“戳刺和释放”方法不会留下有生物危害的锐利医疗废物，并且能够快速释放药物。“戳刺和溶胀 R 型”可以看作是“戳刺和流动”和“戳刺和贴片”方法的结合，而“戳刺和溶胀 I 型”是“包衣和戳刺”和“戳刺和释放”方法之间的一种方法。胰岛素 MN 有望用于无痛糖尿病治疗，为解决包括药物负载、PK/PD 谱、储存和胰岛素 MN 安全性在内的基本问题而进行的额外努力将加速临床转化。
