小柯机器人

美国麻省理工学院Traverso, Giovanni小组近日取得一项新成果。他们报道了可利用胃自动注射器口服递送的全身性单克隆抗体、肽和小分子。相关论文于2021年8月30日发表在《自然-生物技术》杂志上。

在本研究中，研究人员设计了一种口服液体自动注射器，能够输送高达4毫克剂量的生物可利用药物，并具备注射所拥有的快速药代动力学，在注射30分钟后，药物在体内可达到80%的绝对生物利用度和最大血浆药物浓度。这种方法比研究人员之前设计的注射器胶囊剂量效率和药代动力学提高了一个数量级，比临床可用和临床前化学渗透增强技术提高了两个数量级。

研究人员对猪进行胶囊给药，以提供四种常用注射药物的临床相关剂量，包括阿达木单抗、GLP-1 类似物、重组人胰岛素和肾上腺素。在清醒动物模型中的多日给药实验和口服给药数据提供了该系统的转化潜力。

据了解，口服给药是一种简单且非侵入性的给药方法。然而，由于胃肠道吸收差和酶促降解，必需使用胃肠外注射多种分子才能达到所需的剂量和药代动力学。

附：英文原文

Title: Oral delivery of systemic monoclonal antibodies, peptides and small molecules using gastric auto-injectors

Author: Abramson, Alex, Frederiksen, Morten Revsgaard, Vegge, Andreas, Jensen, Brian, Poulsen, Mette, Mouridsen, Brian, Jespersen, Mikkel Oliver, Kirk, Rikke Kaae, Windum, Jesper, Hublek, Frantiek, Water, Jorrit J., Fels, Johannes, Gunnarsson, Stefn B., Bohr, Adam, Straarup, Ellen Marie, Ley, Mikkel Wennemoes Hvitfeld, Lu, Xiaoya, Wainer, Jacob, Collins, Joy, Tamang, Siddartha, Ishida, Keiko, Hayward, Alison, Herskind, Peter, Buckley, Stephen T., Roxhed, Niclas, Langer, Robert, Rahbek, Ulrik, Traverso, Giovanni

Issue&Volume: 2021-08-30

Abstract: Oral administration provides a simple and non-invasive approach for drug delivery. However, due to poor absorption and swift enzymatic degradation in the gastrointestinal tract, a wide range of molecules must be parenterally injected to attain required doses and pharmacokinetics. Here we present an orally dosed liquid auto-injector capable of delivering up to 4-mg doses of a bioavailable drug with the rapid pharmacokinetics of an injection, reaching an absolute bioavailability of up to 80% and a maximum plasma drug concentration within 30min after dosing. This approach improves dosing efficiencies and pharmacokinetics an order of magnitude over our previously designed injector capsules and up to two orders of magnitude over clinically available and preclinical chemical permeation enhancement technologies. We administered the capsules to swine for delivery of clinically relevant doses of four commonly injected medications, including adalimumab, a GLP-1 analog, recombinant human insulin and epinephrine. 

DOI: 10.1038/s41587-021-01024-0

Source: https://www.nature.com/articles/s41587-021-01024-0

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