Thrombin-loaded magnetic microbubbles for the treatment of pseudoaneurysms

The drive toward minimally invasive surgery has yielded multiple benefits for patients but has also increased the incidence of pseudoaneurysms (PSA). The current standard of care is ultrasound-guided thrombin injection to coagulate blood in the PSA sac and seal the ruptured vessel. There is, however, a risk of downstream thrombosis if thrombin escapes into the communicating vessel and this limits patient eligibility for thrombin injection. In this study, the feasibility of using magnetic targeting to reduce the risk of distal thrombosis is investigated. Thrombin-loaded magnetic microbubbles are formulated and injected into tissue-mimicking phantoms of PSAs with different geometries using either saline or whole (equine) blood. Ultrasound imaging is used to quantify the concentration of bubbles remaining in the sac with and without application of a custom-built magnetic array. An absorbance-based assay is also used to quantify the concentration of thrombin escaping from the sac. Magnetic targeting enables a significant increase in thrombin retention in all femoral artery PSA models except one, with up to 97% ± 2.5% of the injected thrombin being retained. It is also confirmed that the enzymatic activity of thrombin is maintained, and that clot formation can be successfully achieved in whole blood.