Researchers at MIT have found the ideal size for injectable nanoparticles that could slow traumatic internal bleeding, buying more time for a patient to reach a hospital for further treatment.
In a rat study, the researchers showed that polymer nanoparticles particles in an intermediate size range, (about 150nm in diameter) were the most effective at stopping bleeding. These particles also were much less likely to travel to the lungs or other off-target sites, which larger particles often do. The results were published in ACS Nano.
“With nano systems, there is always some accumulation in the liver and the spleen, but we’d like more of the active system to accumulate at the wound than at these filtration sites in the body,” said senior author Paula Hammond, Professor at MIT.
Nanoparticles that can stop bleeding, also called haemostatic nanoparticles, can be made in a variety of ways. One of the most commonly used strategies is to create nanoparticles made of a biocompatible polymer conjugated with a protein or peptide that attracts platelets, the blood cells that initiate blood clotting.
In this study, the researchers used a polymer known as PEG-PLGA, conjugated with a peptide called GRGDS, to make their particles. Most of the previous studies of polymeric particles to stop bleeding have focused on particles ranging in size from 300–500nm. However, few, if any studies have systematically analysed how size affects the function of the nanoparticles.
“We were really trying to look at how the size of the nanoparticle affects its interactions with the wound, which is an area that hasn’t been explored with the polymer nanoparticles used as haemostats before,” Hong says.
Studies in animals have shown that larger nanoparticles can help to stop bleeding, but those particles also tend to accumulate in the lungs, which can cause unwanted clotting there. In the new study, the MIT team analysed a range of nanoparticles, including small (< 100nm), intermediate (140–220nm), and large (500–650nm).
They first analysed the nanoparticles in the lab to see how how they interacted with platelets in various conditions, to see how well platelets bound to them. They found that, flowing through a tube, the smallest particles bound best to platelets, while the largest particles stuck best to surfaces coated with platelets. However, in terms of the ratio particles to platelets, the intermediate-sized particles were the lowest.
“If you attract a bunch of nanoparticles and they end up blocking platelet binding because they clump onto each other, that is not very useful. We want platelets to come in,” said lead author, Celestine Hong, an MIT graduate student. “When we did that experiment, we found that the intermediate particle size was the one that ended up with the greatest platelet content.”
The researchers injected the different size classes of nanoparticles into mice to see how long they would circulate for, and where they would end up in the body. As with previous studies, the largest nanoparticles tended accumulated in the lungs or other off-target sites.
The researchers then used a rat model of internal injury to study which particles would be most effective at stopping bleeding. They found that the intermediate-sized particles appeared to work the best, and that those particles also showed the greatest accumulation rate at the wound site.
“This study suggests that the bigger nanoparticles are not necessarily the system that we want to focus on, and I think that was not clear from the previous work. Being able to turn our attention to this medium-size range can open up some new doors,” Prof Hammond said.
The researchers now hope to test these intermediate-sized particles in larger animal models, to get more information on their safety and the most effective doses. They hope that eventually, such particles could be used as a first line of treatment to stop bleeding from traumatic injuries long enough for a patient to reach the hospital.
