Deep eutectic solvents@enteric technology for orally delivering anticoagulant macromolecule drug

Low-molecular-weight heparin (LMWH) is one of the most clinically used anticoagulants to improve venous circulation. However, LMWH requires repeated injections, leading to poor medication compliance. Herein, we developed a deep eutectic solvents (DESs)@enteric technology, an intestinal absorption promotion platform, for the oral administration of LMWH. DESs with geranic acid (Ge) and choline (Ch) were first synthesized and characterized. Then, the DES-LMWH complex was prepared with a DES2:1 (Ge and Ch in a 2:1 molar ratio), demonstrating superior intestinal absorption and high biocompatibility. Finally, DES-LMWH was granulated and loaded into an enteric capsule. In vitro, DESs reversibly opened the tight junctions between intestinal epithelial cells, facilitating the paracellular transport of LMWH. In vivo, the DES-LMWH oral enteric capsule demonstrated an absolute bioavailability of 19.93%, reaching the venous thromboembolism (VTE) prophylaxis threshold and reducing the embolization area by 52.01% in a FeCl3-induced rat femoral venous thrombosis model. In conclusion, DES@enteric technology effectively enhances the oral absorption of LMWH and holds promising translational potential.