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

Area of Science:

• Biomedical Engineering
• Drug Delivery
• Pharmacology

Background:

• Low-molecular-weight heparin (LMWH) is a critical anticoagulant for venous circulation but requires injections, limiting patient compliance.
• Oral administration of LMWH is highly desirable to overcome injection-related challenges.

Purpose of the Study:

• To develop an oral delivery system for LMWH using deep eutectic solvents (DESs)@enteric technology.
• To enhance intestinal absorption and bioavailability of LMWH for potential venous thromboembolism prophylaxis.

Main Methods:

• Synthesized and characterized geranic acid (Ge) and choline (Ch) based DESs.
• Prepared a DES-LMWH complex (DES_2:1) and formulated it into an enteric-coated capsule.
• Evaluated *in vitro* intestinal epithelial tight junction modulation and *in vivo* oral bioavailability and antithrombotic efficacy in a rat model.

Main Results:

• DESs demonstrated reversible opening of intestinal epithelial tight junctions, facilitating LMWH paracellular transport.
• The oral DES-LMWH capsule achieved an absolute bioavailability of 19.93% in rats.
• A significant reduction in venous thrombosis embolization area (52.01%) was observed, meeting the VTE prophylaxis threshold.

Conclusions:

• DES@enteric technology represents a viable platform for enhancing oral LMWH absorption.
• This approach shows significant potential for improving anticoagulant therapy compliance and efficacy.
• The developed oral LMWH formulation holds promise for clinical translation in managing venous thromboembolism.