PEGylated liposomes reduced the transplacental permeability of warfarin while enhancing its anticoagulation effect

Currently, anticoagulation management during pregnancy is still a challenge since there is no optimal anticoagulant drug or regimen that can simultaneously minimize the risks for both the mother and fetus, while delivering warfarin through nanoparticles seems to be a highly promising approach for ensuring the safety of both the mother and fetus. This study constructed a PEGylated liposome loaded with warfarin, and its ability to reduce the transplacental permeability of warfarin while ensuring the anticoagulation effect was tested at both the cellular and animal levels. It was proved that the enlarged particle size (over 300 nm) significantly reduced the internalization of liposomes by placental cells, and the PEGylated liposome encapsulation significantly reduced the transplacental permeability of warfarin in both in vitro and in vivo experiments. The fetal warfarin blood concentration and fetal-maternal ratio were significantly reduced (free warfarin group vs. liposome group: fetal warfarin blood concentration = 17.09 ± 0.91 µg mL^-1vs. 12.60 ± 1.14 µg mL^-1, P < 0.05; fetal-maternal ratio = 1.51 ± 0.16 vs. 0.96 ± 0.38, P < 0.05), while the anticoagulation effect was significantly enhanced (free warfarin group vs. liposome group: PT-INR = 2.26 ± 0.23 vs. 3.21 ± 0.93, P < 0.05). Overall, this study illustrated the potential of the large-particle-sized PEGylated liposomes to balance the fetal toxicity risk and maternal anticoagulation effect of warfarin, thus offering a prospective solution for the anticoagulation dilemma during pregnancy.