After tests run on human blood in laboratory conditions, researchers found that certain nanocapsules could help reduce dangerous side effects of blood clot drugs and potentially make it more effective at lower doses.
A team from the Imperial College London discovered that encasing a tissue plasminogen activator (tPA), a blood clot-dissolving drug, in especially fabricated nanocapsules. This allows the drug to be delivered in a more targeted manner, directly to harmful blood clots, in an increased circulation time.
Researchers presented their findings in the report "Fibrinogen-mimicking, multiarm nanovesicles for human thrombus-specific delivery of tissue plasminogen activator and targeted thrombolytic therapy," appearing in the latest Science Advances.
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Fighting Blood Clots and Its Risks
Blood clots, known as thrombi, could occur in situ within the human's vascular system, impeding blood flow. It occurs when blood cells called platelets are activated and linked together, similar to what they do in healing wounds. The platelets connect to each other through proteins called fibrinogen, which serve as bridges between the blood cells.
It is a key cause of strokes and heart attacks, which are among the leading causes of death worldwide. Blood clots could be cured through the use of tPA, dissolving clots and clearing the blood vessel, returning the blood flow to normal.
However, the use of tPA has dangerous side effects, one of which is off-target internal bleeding. A 2015 report published in the Journal of Drug Design and Research notes that tPA use also induces matrix degradation and promotes tissue fibrosis or the scarring of tissues. Additionally, the drug's circulation time is notoriously short, which requires repeated doses in medication. Unfortunately, more doses mean more chances for the side effects to take place.
These side effects have largely limited the medical use of tPA, being used nowadays for only a small section of patients that have been tested to be eligible.
Wrapping tPA in Nanocapsules
In the new study, tPA is kept inside nanocapsules designed to attach themselves to activated platelets that are present in blood clots. Here they release their tPA payload and dissolve clots right at the site of the blockage.
"tPA has a narrow window between desired effect and side effects, so we have wrapped it in a package that extends this therapeutic window and minimizes the required dose. Our results are exciting but animal and clinical studies are required for validation," explains Dr. Rongjun Chen from the Department of Chemical Engineering at the Imperial College in its news release.
The new nanocapsule, known as tPA-cRGD-PEG-NV, mimics the behavior of fibrinogen in order to find out where clotting occurs in the vascular system. Researchers first tested it on healthy human blood under static laboratory conditions, administering the nanocapsules in samples in petri dishes and in physiological flow conditions that mimic blood flow in humans. To test the blood flow conditions, researchers developed a computer model that simulates encapsulated tPA behavior along circulating blood.
Researchers discovered that the nanocapsules were highly selective, binding only to activated plates and dissolving clots in the same timeframe as unencapsulated tPA.
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