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 30 min 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. These multi-day dosing experiments and oral administration in awake animal models support the translational potential of the system.

口服给药为药物递送提供了一种简单且无创的方法。然而，由于胃肠道吸收不良和酶促降解迅速，必须肠胃外注射多种分子才能达到所需的剂量和药代动力学。在这里，我们展示了一种口服给药液体自动注射器，能够以注射剂的快速药代动力学递送高达 4 mg 剂量的生物利用度药物，在注射后 30 分钟内达到高达 80% 的绝对生物利用度和最大血浆药物浓度给药。与我们之前设计的注射器胶囊相比，这种方法将给药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。我们将胶囊用于猪，以提供临床相关剂量的四种常用注射药物，包括阿达木单抗、GLP-1 类似物、重组人胰岛素和肾上腺素。这些在清醒动物模型中进行的多天给药实验和口服给药支持了该系统的转化潜力。