Combining a novel peptide with the commonly used blood thinner heparin can improve treatment for blood clots, according to a new US study.
Heparin is prescribed for patients with blood clotting disorders or after surgery to prevent complications. However, it is difficult to dose correctly, potentially leading to overdosing or underdosing.
Now scientists at Penn State University, Pennsylvania, have combined the anticoagulant with a peptide – a protein fragment – to see if it would slow down the release of the drug and concentrate the activity of the medication directly at the site of a clot.
Dr Scott Medina, Penn State associate professor of biomedical engineering, said: “We wanted to develop a material that can gradually deliver heparin over time rather than the current iteration that gets cleared from the body in a couple of hours.
“We also wanted to deliver the drug through the skin instead of through an IV.”
Writing in the journal Small, they say when mixed, positively charged peptides and negatively charged heparin bind to create a nanogranular paste that can be injected under the skin. This is diffused in the circulatory system and travels to blood clots.
The turbulent flow of fluid near a blood clot triggers the two materials to separate, allowing heparin to begin its anticoagulating action.
First author Atip Lawanprasert said: “The peptide is ideal for pairing with heparin because it essentially blocks heparin’s action until it is needed in the body.
“The peptide also has some anticoagulating properties on its own: It binds to platelets in the blood, enabling action at the clotting site.”
Without an added bonding agent, heparin applies its anti-clotting properties indiscriminately, not just at blood clot sites, and clears within 60-90 minutes.
However, preclinical animal trials showed that adding the peptide increases heparin’s half-life to almost 24 hours.
Dr Medina said: “The increased half-life allows for sustained treatments for patients, less medication waste and more accurate dosing. Eventually, this could allow the medication to be injected under the skin just once a day, rather than an all-day IV drip.”
The research team now hopes to replicate the study in a clinical setting, as well as study the effect of the medication’s toxicity in the body if administered over multiple days.
Source:
Lawanprasert A, Pimcharoen S, Sumner SE, Watson CT, Manning KB, Kirimanjeswara GS, Medina SH. (2022) “Heparin-Peptide Nanogranules for Thrombosis-Actuated Anticoagulation.” Small, doi: 10.1002/smll.202203751
Link: https://onlinelibrary.wiley.com/doi/10.1002/smll.202203751
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