Pills are a cornerstone of medicine but can be challenging to swallow. While liquid formulations are easier to ingest, they lack the capacity to localize therapeutics with excipients nor act as controlled release devices. Here we describe drug formulations based on liquid in situ-forming tough (LIFT) hydrogels that bridge the advantages of solid and liquid dosage forms. LIFT hydrogels form directly in the stomach through sequential ingestion of a crosslinker solution of calcium and dithiol crosslinkers, followed by a drug-containing polymer solution of alginate and four-arm poly(ethylene glycol)-maleimide. We show that LIFT hydrogels robustly form in the stomachs of live rats and pigs, and are mechanically tough, biocompatible and safely cleared after 24 h. LIFT hydrogels deliver a total drug dose comparable to unencapsulated drug in a controlled manner, and protect encapsulated therapeutic enzymes and bacteria from gastric acid-mediated deactivation. Overall, LIFT hydrogels may expand access to advanced therapeutics for patients with difficulty swallowing.

药片是医学的基石，但吞咽起来却很困难。虽然液体制剂更容易摄入，但它们缺乏用赋形剂进行局部治疗的能力，也不能充当控释装置。在这里，我们描述了基于液体原位形成坚韧（LIFT）水凝胶的药物配方，它结合了固体和液体剂型的优点。通过依次摄入钙和二硫醇交联剂的交联剂溶液，然后摄入海藻酸盐和四臂聚乙二醇-马来酰亚胺的含药聚合物溶液，LIFT水凝胶直接在胃中形成。我们证明，LIFT 水凝胶在活体大鼠和猪的胃中牢固形成，并且机械坚韧、生物相容性好，24 小时后可安全清除。LIFT 水凝胶以受控方式输送与未封装药物相当的总药物剂量，并保护封装的治疗酶和细菌免受胃酸介导的失活。总体而言，LIFT 水凝胶可以扩大吞咽困难患者获得先进治疗的机会。