Abstract:

Heparin has been used as anti-thrombotic agents clinically. In this work, the copolymer based on hydrophilic heparin and hydrophobic deoxycholic acid(hep-DOCA, HD) was synthesized. Indometacin(IDM)-loaded HD micelles were prepared through aqueous self-assembly to enhance the anti-thrombotic capability of micelles synergistically and characterized by dynamic light scattering, Zeta potential and transmission electron microscopry(TEM). When the drug content of the nanomicelles was 0.0913 g/L, the concentration of the drug-loaded nanomicelle was 0.4 g/L, and the cell survival rate and hemolysis rate were 92.81% and 0.83%, indicating that the drug-loaded nanomicelles had good biocompatibility. The whole blood coagulation indexes of heparin sodium, hep-DOCA and HD-IDM were 86.48%, 77.47% and 89.53%, respectively. The whole blood coagulation time was 927, 837 and 965 s, respectively. The thrombus mass produced in the thrombus clotting experiment was 0.11, 0.20 and 0.07 g, respectively, which confirmed that the drug-loaded nanomicelles had excellent anticoagulant effect.

Key words: heparin, deoxycholic acid, micelles, indomethacin, anticoagulant