Synthesis and evaluation of drug-loaded silver nanoparticles as hemostatic agents to halt uncontrolled bleeding

Objective: The aim of this research study was to formulate a cost-effective, stable, less toxic and more efficacious intravenous nanoformulation that could rapidly augment the process of hemostasis. Significance: Silver nanoparticles (AgNPs) evoked platelet activation, whereas alum (AM) neutralized the plasma proteins, causing blood coagulation. Tranexamic acid (TA) inhibited fibrinolysis and stabilized the formed blood clot. Methods: The nanoformulation (NF) was subjected to characterization techniques such as UV-Vis spectrophotometry, FTIR, XRD, TGA and DSC analysis, which elucidated successful drug conjugation. Results: Zeta-sizing confirmed the particle size of NF to be 256.6 nm with 0.497 PDI and a zeta potential of + 9.24 mV. In-vitro release profile exhibited first-order kinetics, indicating sustained release, conferring sustained release of NF for 12 h. NF was hemocompatible at the tested doses, as its extent of hemolysis was < 0.8% and < 1%, following EU and FDA guidelines, respectively. Ex-vivo studies revealed that NF recorded the highest viscosity, i.e. 36.5 cP, and maximum mass of clotted blood, i.e. 17.4 mg, in comparison to other combinations. In-vivo studies indicated a 100-fold dose reduction, i.e. 0.1 mg/kg, compared to the marketed formulation, Transamin (R), i.e. 10 mg/kg. 10 folds dose reduction, i.e. 1 mg/kg, exhibited more efficacious results than Transamin (R), owing to the synergistic effect and nano-sizing of components. Conclusion: A safe, cost-effective, and relatively less toxic hemostatic nanoparticles were formulated, that can be intravenously administered to halt bleeding within seconds.