Nanotechnology - Driven Innovations in Anticoagulant Delivery andAntidote Development for Hemostasis Regulation

Introduction: Hemostasis is a complex physiological mechanism that maintains normal blood flow and prevents excessive bleeding after vascular injury. Anticoagulant drugs are widely used to prevent systemic embolism, stroke, and recurrent venous thromboembolism (VTE). Conventional therapies such as heparins and vitamin K antagonists (VKAs) face challenges including parenteral administration, toxicity, and poor patient compliance, leading to an increased need for innovative delivery systems and reversal strategies. Methods: This review synthesises current evidence on nanotechnology-driven drug delivery systems (DDS) and antidote development for anticoagulants, drawing from recent preclinical and clinical studies. The focus is on liposomes, ethosomes, cubosomes, hydrogels, solid lipid nanoparticles (SLnPs), self-nanoemulsifying drug delivery systems (SNEDDS), and emerging antidotes such as idarucizumab, andexanet alfa, and ciraparantag. Results: Nanocarrier systems enhance anticoagulant therapy by improving solubility, stability, targeted delivery, and sustained release. Oral DDS approaches, including solid dispersions, fastdissolving platforms, and SNEDDS, show potential to replace invasive parenteral regimens. Antidote development has advanced rapidly, with idarucizumab approved for dabigatran reversal, andexanet alfa for factor Xa inhibitors, and ciraparantag demonstrating broad-spectrum activity in development. Discussion: Nanotechnology-based DDS address long-standing limitations of conventional anticoagulants, improving patient compliance and therapeutic safety. However, cost, immunogenicity, clearance pathways, and regulatory challenges remain barriers to widespread adoption. Antidotes, while effective, raise concerns about accessibility and affordability in low-resource settings. Conclusion: This review highlights the novelty of integrating nanotechnology-based delivery systems with targeted antidote strategies. Such convergence offers a patient-centred, safer, and more effective framework for anticoagulant therapy, while underscoring the need for future research in clinical translation, cost-effectiveness, and long-term safety.