Blood Clotting & Drug Delivery
Micron-Sized Drug Vehicle for Unregulated Blood Clotting
Every time you cut or injure yourself, damaging a blood vessel, a process known as the clotting cascade or coagulation is jump started in your body. The injured blood vessel leaks blood, which activates your platelets, disk-shaped cell fragments dispersed throughout your blood, to release a series of enzymes including thrombin. Subsequently, thrombin helps convert fibrinogen, a protein molecule that plays a primary role in clotting, into fibrin. The fibrin then binds to itself, forming a blood clot and closing the wound. Researchers at the joint Emory University and Georgia Tech Wallace H. Coulter Department of Biomedical Engineering have found a way to leverage this natural clotting cascade to create a targeted drug delivery vehicle.
This drug vehicle is a polymer shell containing fibrinogen that can encapsulate a range of different drugs, which treat various conditions occurring in areas where blood vessels have been injured. Due to fibrinogen’s natural role in the clotting cascade, the patient’s own platelets (cell fragments involved in clot formation) bind to the surface fibrinogen. This fibrinogen/platelet shell allows the drugs it carries to travel and target injury sites. If an injury occurs, thrombin released into the patients’ blood stream will convert the fibrinogen contained in the shell to fibrin which then can be incorporated into the clot. This reaction consequently makes the platelets on the shell contract like a muscle, which rips open the shell and releases the drug directly into the targeted injury site.
Caroline Hansen, PhD, GA Tech graduate student, one of the researchers developing this drug delivery vehicle, said “We are essentially leveraging a patient’s own healthy pathways to affect targeted drug delivery. This is unique because many other current methods used to clinically target a drug to a disease site use external magnets, lasers or devices. We don’t have to do that because the platelet cells, which release fibrinogen attracting enzymes, are doing it for us.”
Injury site specific drug targeting is essential to the efficacy and success of many treatments. Without this targeting, a patient’s entire body, including organs, are exposed to any drug that is delivered into their blood stream. This method of drug application can lead to many off-target and adverse side effects. Furthermore, it exposes a patient’s entire body to the active ingredient of a drug, which is ideally are only meant to be applied to a specific target. This can have injurious impacts on non-target body systems as well as decrease the therapeutic efficacy of the drug on the injury site.
This drug delivery technology can potentially be paired with a variety of drugs to treat a range of conditions related to excessive bleeding or over clotting. These include hemophilia, heart attacks and strokes related to transient blood clots, deep vein thrombosis, pulmonary embolism, and certain varieties of cancer.
Currently, the research team is focusing on applying this drug vehicle technology to the treatment of hemophilia, a genetic disorder that impairs a patient’s ability to create blood clots. “30% of severe hemophilia patients have developed anti-bodies to the primary drug that is used to treat this disorder,” explain Hansen. “Their body identifies the drug as a foreign substance causing their antibodies attack it and render it inactive. But by encapsulating this hemophilia drug in our micro capsule, the patient’s platelets can bind with it. They then carry the drug to the sight of bleeding and break it open to deliver the medication to the injured area, thereby protecting the drug from the patient’s antibodies.”
Ultimately Hansen and her colleagues envision potentially taking the technology into a startup company and potentially partnering with other pharmaceutical companies that are developing therapies that this technology could deliver. Cliff Michaels, the assistant director at Emory’s Office of Technology Transfer, said “I think a possible avenue that would be interesting would be to find a commercial partner who has a drug in development but needs help getting it to the right site. Many drugs may not be efficacious enough to move on to a clinical trial because of their inability to target a certain site. This might be a technology that can be partnered with one of those to improve the efficacy of their drug and overcome the hurdles that they have faced in its development.” Though the final clinical application of this drug delivery technology is not entirely clear, it appears to hold much promise for the future.
The research team consists of Caroline Hansen, PhD, GA Tech graduate student, Wilbur Lam, PhD and Yumiko Sakurai from Emory, and Andrew Lyon from Chapman University.
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