To shed more light on those aspects, MIT chemical engineers have now performed the first methodical research study of how different-sized polymer nanoparticles flow in the body and engage with platelets, the cells that promote blood clotting.
A brand-new analysis offers assistance on the size of nanoparticles that might be most efficient at stopping internal bleeding. Credit: Christine Daniloff, MIT
A new analysis offers guidance on the size of nanoparticles that might be most reliable at stopping internal bleeding.
Terrible injuries are the leading cause of death in the U.S. amongst individuals 45 and under, and such injuries represent more than 3 million deaths each year worldwide. To reduce the death toll of such injuries, many researchers are dealing with injectable nanoparticles that can home in on the website of an internal injury and attract cells that assist to stop the bleeding till the patient can reach a medical facility for further treatment.
While a few of these particles have shown guarantee in animal research studies, none have been checked in human patients yet. One factor for that is an absence of details regarding the mechanism of action and possible security of such particles. To shed more light on those factors, MIT chemical engineers have now performed the very first organized study of how different-sized polymer nanoparticles circulate in the body and engage with platelets, the cells that promote blood clot.
In a research study of rats, the scientists revealed that particles in an intermediate size variety, around 150 nanometers in diameter, were the most reliable at stopping bleeding. These particles likewise were much less likely to take a trip to the lungs or other off-target sites, which larger particles frequently do.
” With nano systems, there is constantly some build-up in the liver and the spleen, however we d like more of the active system to collect at the injury than at these purification sites in the body,” states Paula Hammond, an MIT Institute Professor, head of the Department of Chemical Engineering, and a member of MITs Koch Institute for Integrative Cancer Research.
Hammond; Bradley Olsen, the Alexander and I. Michael Kasser Professor of Chemical Engineering; and George Velmahos, a teacher of surgical treatment at Harvard Medical School and chief of injury, emergency surgical treatment, and surgical crucial care at Massachusetts General Hospital, are the senior authors of the study.
MIT graduate student Celestine Hong is the lead author of the paper, which appears in the journal ACS Nano.
Size impacts
Nanoparticles that can stop bleeding, likewise called hemostatic nanoparticles, can be made in a range of methods. Among the most typically utilized techniques is to produce nanoparticles made of a biocompatible polymer conjugated with a protein or peptide that brings in platelets, the blood cells that start blood clot.
In this study, the researchers utilized a polymer known as PEG-PLGA, conjugated with a peptide called GRGDS, to make their particles. The majority of the previous research studies of polymeric particles to stop bleeding have actually concentrated on particles varying in size from 300 to 500 nanometers. Few, if any research studies have systematically evaluated how size impacts the function of the nanoparticles.
” We were really attempting to look at how the size of the nanoparticle impacts its interactions with the wound, which is an area that hasnt been checked out with the polymer nanoparticles used as hemostats previously,” Hong states.
Research studies in animals have actually revealed that bigger nanoparticles can assist to stop bleeding, however those particles also tend to accumulate in the lungs, which can trigger undesirable clotting there. In the brand-new research study, the MIT group analyzed a variety of nanoparticles, including small (less than 100 nanometers), intermediate (140 to 220 nanometers), and big (500 to 650 nanometers).
First, they analyzed the particles in the laboratory, to study how they connect with active platelets under a range of conditions. One of their tests measured how well the particles bound to platelets as the platelets streamed through a tube. In this test, the tiniest nanoparticles led to the greatest percentage of bound platelets. In another test, they measured how well nanoparticles could stick to a surface covered in platelets. In this scenario, the biggest nanoparticles stuck the best.
Then, the researchers asked a slightly various concern and evaluated how much of the mass adhered to the surface area was nanoparticles and how much was platelets, due to the fact that the ultimate goal is to bring in as lots of platelets as possible. Using that standard, they found that the intermediate particles were the most efficient.
” If you draw in a lot of nanoparticles and they wind up blocking platelet binding since they clump onto each other, that is not really beneficial. We want platelets to come in,” Hong says. “When we did that experiment, we discovered that the intermediate particle size was the one that wound up with the best platelet material.”
Stopping the bleeding
The researchers then tested the 3 size classes of nanoparticles in mice. First, they injected the particles in healthy mice to study the length of time they would circulate in the body and where they would collect. They found that, as seen in prior studies, the biggest particles were more likely to collect in the lungs or other off-target sites, and their flow time was shorter.
Working with their collaborators at MGH, the scientists then used a rat model of internal injury to study which particles would be most efficient at stopping bleeding. They found that the intermediate-sized particles appeared to work the best, which those particles likewise showed the best build-up rate at the injury website.
” This study recommends that the bigger nanoparticles are not necessarily the system that we wish to concentrate on, and I believe that was not clear from the previous work. Being able to turn our attention to this medium-size range can open some new doors,” Hammond says.
The researchers now wish to check these intermediate-sized particles in bigger animal designs, to get more details on their security and the most reliable dosages. They hope that eventually, such particles might be used as a first line of treatment to stop bleeding from terrible injuries long enough for a patient to reach the healthcare facility.
” These particles are suggested to deal with preventable deaths. Theyre not a cure-all for internal bleeding, however theyre implied to provide a person a couple of extra hours until they can get to a health center where they can receive adequate treatment,” Hong states.
Reference: “Modulating Nanoparticle Size to Understand Factors Affecting Hemostatic Efficacy and Maximize Survival in a Lethal Inferior Vena Cava Injury Model” by Celestine Hong, Osaid Alser, Anthony Gebran, Yanpu He, Wontae Joo, Nikolaos Kokoroskos, George Velmahos, Bradley D. Olsen and Paula T. Hammond, 28 January 2022, ACS Nano.DOI: 10.1021/ acsnano.1 c09108.
The research study was moneyed by the U.S. Army Research Office through the Institute for Soldier Nanotechnologies at MIT, and the Department of Defense.
Few, if any studies have actually methodically evaluated how size impacts the function of the nanoparticles.
In this test, the smallest nanoparticles resulted in the biggest percentage of bound platelets. In another test, they determined how well nanoparticles could stick to a surface area coated in platelets. The scientists then checked the 3 size classes of nanoparticles in mice.