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Findings may aid drug delivery, bioimaging

Fluorescence microscope used

to illuminate microfluidic device

simulating a blood vessel.

Photo from Anson Ma/UConn

A study published in Biophysical Journal has revealed new information about how particles behave in the bloodstream, and investigators believe the findings have implications for bioimaging and targeted drug delivery in cancer.

The investigators used a microfluidic channel device to observe, track, and measure how individual particles behave in a simulated blood vessel.

Their goal was to learn more about the physics influencing a particle’s behavior as it travels in the blood and to determine which particle size might be the most effective for delivering drugs to their targets.

“Even before particles reach a target site, you have to worry about what is going to happen with them after they get injected into the bloodstream,” said study author Anson Ma, PhD, of the University of Connecticut in Storrs, Connecticut.

“Are they going to clump together? How are they going to move around? Are they going to get swept away and flushed out of our bodies?”

Using a high-powered fluorescence microscope, Dr Ma and his colleagues were able to observe particles being carried along in the simulated blood vessel in what could be described as a vascular “Running of the Bulls.”

Red blood cells raced through the middle of the channel, and the particles were carried along in the rush, bumping and bouncing off the blood cells until they were pushed to open spaces—called the cell-free layer—along the vessel’s walls.

The investigators found that larger particles—the optimum size appeared to be about 2 microns—were most likely to get pushed to the cell-free layer, where their chances of carrying a drug to a targeted site are greatest.

The team also determined that 2 microns was the largest size that should be used if particles are going to have any chance of going through the leaky blood vessel walls to the site.

“When it comes to using particles for the delivery of cancer drugs, size matters,” Dr Ma said. “When you have a bigger particle, the chance of it bumping into blood cells is much higher, there are a lot more collisions, and they tend to get pushed to the blood vessel walls.”

These results were somewhat surprising. The investigators had theorized that smaller particles would probably be the most effective since they would move the most in collisions with blood cells.

But the opposite proved true. The smaller particles appeared to skirt through the mass of moving blood cells and were less likely to get bounced to the cell-free layer.

Knowing how particles behave in the circulatory system should help improve targeted drug delivery, Dr Ma said. And this should further reduce the side effects caused by potent cancer drugs missing their target.

Measuring how different sized particles move in the bloodstream may also be beneficial in bioimaging, where the goal is to keep particles circulating in the bloodstream long enough for imaging to occur. In that case, smaller particles would be better, Dr Ma said.

Moving forward, Dr Ma would like to explore other aspects of particle flow in the circulatory system, such as how particles behave when they pass through a constricted area, like from a blood vessel to a capillary.

Capillaries are only about 7 microns in diameter. Dr Ma said he would like to know how that constricted space might impact particle flow or the ability of particles to accumulate near the vessel walls.

“We have all of this complex geometry in our bodies,” Dr Ma said. “Most people just assume there is no impact when a particle moves from a bigger channel to a smaller channel because they haven’t quantified it. Our plan is to do some experiments to look at this more carefully, building on the work that we just published.”

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Fluorescence microscope used

to illuminate microfluidic device

simulating a blood vessel.

Photo from Anson Ma/UConn

A study published in Biophysical Journal has revealed new information about how particles behave in the bloodstream, and investigators believe the findings have implications for bioimaging and targeted drug delivery in cancer.

The investigators used a microfluidic channel device to observe, track, and measure how individual particles behave in a simulated blood vessel.

Their goal was to learn more about the physics influencing a particle’s behavior as it travels in the blood and to determine which particle size might be the most effective for delivering drugs to their targets.

“Even before particles reach a target site, you have to worry about what is going to happen with them after they get injected into the bloodstream,” said study author Anson Ma, PhD, of the University of Connecticut in Storrs, Connecticut.

“Are they going to clump together? How are they going to move around? Are they going to get swept away and flushed out of our bodies?”

Using a high-powered fluorescence microscope, Dr Ma and his colleagues were able to observe particles being carried along in the simulated blood vessel in what could be described as a vascular “Running of the Bulls.”

Red blood cells raced through the middle of the channel, and the particles were carried along in the rush, bumping and bouncing off the blood cells until they were pushed to open spaces—called the cell-free layer—along the vessel’s walls.

The investigators found that larger particles—the optimum size appeared to be about 2 microns—were most likely to get pushed to the cell-free layer, where their chances of carrying a drug to a targeted site are greatest.

The team also determined that 2 microns was the largest size that should be used if particles are going to have any chance of going through the leaky blood vessel walls to the site.

“When it comes to using particles for the delivery of cancer drugs, size matters,” Dr Ma said. “When you have a bigger particle, the chance of it bumping into blood cells is much higher, there are a lot more collisions, and they tend to get pushed to the blood vessel walls.”

These results were somewhat surprising. The investigators had theorized that smaller particles would probably be the most effective since they would move the most in collisions with blood cells.

But the opposite proved true. The smaller particles appeared to skirt through the mass of moving blood cells and were less likely to get bounced to the cell-free layer.

Knowing how particles behave in the circulatory system should help improve targeted drug delivery, Dr Ma said. And this should further reduce the side effects caused by potent cancer drugs missing their target.

Measuring how different sized particles move in the bloodstream may also be beneficial in bioimaging, where the goal is to keep particles circulating in the bloodstream long enough for imaging to occur. In that case, smaller particles would be better, Dr Ma said.

Moving forward, Dr Ma would like to explore other aspects of particle flow in the circulatory system, such as how particles behave when they pass through a constricted area, like from a blood vessel to a capillary.

Capillaries are only about 7 microns in diameter. Dr Ma said he would like to know how that constricted space might impact particle flow or the ability of particles to accumulate near the vessel walls.

“We have all of this complex geometry in our bodies,” Dr Ma said. “Most people just assume there is no impact when a particle moves from a bigger channel to a smaller channel because they haven’t quantified it. Our plan is to do some experiments to look at this more carefully, building on the work that we just published.”

Fluorescence microscope used

to illuminate microfluidic device

simulating a blood vessel.

Photo from Anson Ma/UConn

A study published in Biophysical Journal has revealed new information about how particles behave in the bloodstream, and investigators believe the findings have implications for bioimaging and targeted drug delivery in cancer.

The investigators used a microfluidic channel device to observe, track, and measure how individual particles behave in a simulated blood vessel.

Their goal was to learn more about the physics influencing a particle’s behavior as it travels in the blood and to determine which particle size might be the most effective for delivering drugs to their targets.

“Even before particles reach a target site, you have to worry about what is going to happen with them after they get injected into the bloodstream,” said study author Anson Ma, PhD, of the University of Connecticut in Storrs, Connecticut.

“Are they going to clump together? How are they going to move around? Are they going to get swept away and flushed out of our bodies?”

Using a high-powered fluorescence microscope, Dr Ma and his colleagues were able to observe particles being carried along in the simulated blood vessel in what could be described as a vascular “Running of the Bulls.”

Red blood cells raced through the middle of the channel, and the particles were carried along in the rush, bumping and bouncing off the blood cells until they were pushed to open spaces—called the cell-free layer—along the vessel’s walls.

The investigators found that larger particles—the optimum size appeared to be about 2 microns—were most likely to get pushed to the cell-free layer, where their chances of carrying a drug to a targeted site are greatest.

The team also determined that 2 microns was the largest size that should be used if particles are going to have any chance of going through the leaky blood vessel walls to the site.

“When it comes to using particles for the delivery of cancer drugs, size matters,” Dr Ma said. “When you have a bigger particle, the chance of it bumping into blood cells is much higher, there are a lot more collisions, and they tend to get pushed to the blood vessel walls.”

These results were somewhat surprising. The investigators had theorized that smaller particles would probably be the most effective since they would move the most in collisions with blood cells.

But the opposite proved true. The smaller particles appeared to skirt through the mass of moving blood cells and were less likely to get bounced to the cell-free layer.

Knowing how particles behave in the circulatory system should help improve targeted drug delivery, Dr Ma said. And this should further reduce the side effects caused by potent cancer drugs missing their target.

Measuring how different sized particles move in the bloodstream may also be beneficial in bioimaging, where the goal is to keep particles circulating in the bloodstream long enough for imaging to occur. In that case, smaller particles would be better, Dr Ma said.

Moving forward, Dr Ma would like to explore other aspects of particle flow in the circulatory system, such as how particles behave when they pass through a constricted area, like from a blood vessel to a capillary.

Capillaries are only about 7 microns in diameter. Dr Ma said he would like to know how that constricted space might impact particle flow or the ability of particles to accumulate near the vessel walls.

“We have all of this complex geometry in our bodies,” Dr Ma said. “Most people just assume there is no impact when a particle moves from a bigger channel to a smaller channel because they haven’t quantified it. Our plan is to do some experiments to look at this more carefully, building on the work that we just published.”

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