Local Infusing Antiplatelet Microspheres to Prevent Thrombosis Post-PCI: a Feasibility Study in Rabbit Aorta

After percutaneous coronary intervention (PCI), dual antiplatelet therapy (DAPT) is required to prevent thrombosis, but systemic DAPT may increase bleeding risk. This study aimed to develop a new concept of antiplatelet therapy administered via local infusion of PLGA-Fe₃O₄-ticagrelor microspheres (PFTm).

PLGA loaded with Fe₃O₄ and ticagrelor magnetic microspheres were constructed. In vitro study, the morphology, relaxation rate, drug release rate, encapsulation efficiency, and biocompatibility of PFTm were evaluated. In vivo study, vascular injury model of rabbit abdominal aorta was established by Fogarty balloon. The injured rabbit aorta wall was infused PFTm by infusion balloon in the local PFTm therapy group, while the rabbit was injected PFTm intravenously in the systemic PFTm therapy group. The non-therapy control group and healthy control group did not receive PFTm treatment. MR T2WI was performed pre-operation, post-operation to detect PFTm distribution. Then, the targeted abdominal aorta segments were harvest for pathological examination.

The PFTm was spherical with a size of 930.5 ± 134 nm and SPAN was 0.35. The ticagrelor encapsulation efficiency was 82% ± 2%, and the release rate reached 88% ± 2% within 96 h. The r2 of the PFTm was 332.0 mM^-1 s^-1. All rabbits were successfully established abdominal aorta injury model. MRI showed significant decrease of SNR in aortic wall which represented PFTm infused into aortic wall. Pathology showed that local thrombus was significant inhibited in the local PFTm therapy group compared with the other groups.

The new concept of releasing drugs in a sustained manner for local antiplatelet therapy after PCI was successfully established.