Image by Andre E.X. Brown
SAN FRANCISCO—Microbubbles can be used to simultaneously treat and monitor thrombosis, according to preclinical research presented at the ATVB/PVD 2015 Scientific Sessions.
The microbubbles double as agents for contrast-enhanced ultrasound imaging and targeted drug-delivery vehicles.
Experiments in mice showed that the microbubbles could deliver treatment directly to a blood clot, noticeably reducing its size without causing abnormal bleeding.
Karlheinz Peter, MD, PhD, of Baker IDI Heart and Diabetes Institute in Melbourne, Victoria, Australia, presented these results at the meeting as abstract 36.
He and his colleagues combined the thrombolytic agent urokinase with an activated-platelet-specific, single-chain antibody and placed the duo on the surface of microbubbles.
The researchers then tracked the microbubbles’ progress in a mouse model of carotid artery thrombosis induced by ferric-chloride.
The team monitored clot size in these mice with ultrasound imaging and measured bleeding time after experimental injury, while comparing 4 treatment groups:
- Microbubbles coated with both the targeting antibody and urokinase
- Targeted microbubbles and a high dose of urokinase administered separately
- Targeted microbubbles and a low dose of urokinase administered separately
- A control group with targeted microbubbles and no urokinase.
Microbubbles with urokinase on their surface significantly reduced clot size after 45 minutes, but microbubbles without urokinase did not. The mean percentage change in thrombus size from baseline was 97.16 ± 4.3 and 37.09 ± 5.6, respectively (P<0.001).
Urokinase administered alone could only match the efficacy of the treatment-loaded microbubbles if the drug was administered at a high dose. However, that significantly prolonged bleeding time from baseline—1079.25 ± 260.7 seconds vs 79.25 ± 6.5 seconds (P<0.001)—whereas, treatment with microbubbles did not.
While this research is in the early stages, the researchers believe the technology could help patients who develop venous thromboembolism and related conditions, such as heart attack and stroke. The team also believes the technology could have a major impact on treatment of patients in the emergency department.
