For drugs, a nano-sized journey through the lungs

By following the movements of tiny particles injected into rat lungs, scientists have created a nanoparticle profile that could help deliver drugs and reduce the toxicity of air pollutants.

By tracing the movements of tiny particles injected into rat lungs, scientists have created a nanoparticle profile that could prove useful in delivering drugs and reducing the toxicity of air pollutants.

Because of the huge surface area of our lungs and the unfettered access they provide to the rest of the body, the pulmonary delivery of nanoparticles is attracting a lot of attention.

In a new Nature Biotechnology study, John Frangioni of Beth Israel Deaconess Medical Center in Boston and Akira Tsuda of Harvard School of Public Health and their colleagues described the behavior of nanoparticles during their first hour after being injected into lungs.

The researchers observed these actions in real-time by using near-infrared (NIR) fluorescence imaging – which provides a highly sensitive detection of nanoparticle trafficking several millimeters deep inside tissue.

To understand the characteristics that control movement throughout the body, the team played around with different particle sizes, shapes, charges, and chemical make-ups. They engineered two types of nanoparticles (one organic and the other an inorganic/organic hybrid) and sized them from 5 to 300 nanometers in diameter. They also gave them varying surface charges: some positive, some negative, and some “zwitterionic” – or electrically neutral with their positive and negative charges balanced.

After administering these particles into the right lung of a Sprague-Dawley male rat using a catheter, the team noticed that most of the nanoparticles stayed in the lungs. But those under 34 nm (the size of some memory chips) that are not positively charged found their way into the lymph nodes within 10 minutes.

The smallest zwitterionic nanoparticles (5 nm) quickly made their way to the lymph nodes within 3 minutes, entered the bloodstream, and about half an hour later, they accumulated in the kidneys and were ultimately excreted out in urine.

“Our results might prove useful to investigators trying to engineer inhaled nanoparticle-based drugs,” the authors wrote. Those designed to these specs could rapidly reach the bloodstream and the unused drugs could be released in urine.

Additionally, future research could focus on chemical strategies that alter the size and charge of air pollutants. Non-positive nanoparticles less than 34 nm are “potentially the most dangerous,” according to the authors, because they could become lodged in the lymph nodes or travel throughout the body, causing inflammation and possibly cancer development.

“We did not know exactly, how much is the size cutoff,’’ Tsuda told the Boston Globe. “Now, we’ve defined the parameters to get a particle into the bloodstream,” Frangioni added.

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