The team tracked the flow of nanoparticles in real time, up to an hour after injection. Tsuda found that size was the most important determinant for passing through the lungs, followed by a nanoparticle’s surface charge. Particles that were smaller than six nanometers and dipolar (both positively and negatively charged) traveled from the lungs to the lymph nodes and into the bloodstream within just a few minutes. These same particles lit up in the kidneys shortly afterward, implying that they could easily be expelled from the body. The findings are published in the latest issue of the journal Nature Biotechnology.
David Edwards, Gordon McKay Professor of the practice of biomedical engineering at Harvard University, sees the group’s findings as a starting blueprint for designing effective vaccines, which are often targeted to the immune cells in lymph nodes. Edwards says their results may provide a molecular explanation for the success of certain vaccines, such as the hepatitis B vaccine, which is made up of molecules within the range of six to 34 nanometers. “This suddenly just clarifies this issue of what exactly is getting into the lymph system and what is possibly getting into the bloodstream,” he says.
“This work paves the way for new therapeutic approaches for not only local delivery to the lungs but also for systemic delivery via pulmonary administration,” says Joseph DeSimone, director of nanomedicine at the University of North Carolina at Chapel Hill.
In the future, Tsuda and his colleagues plan to do similar studies to evaluate nanoparticle behavior from nasal cavities to the brain. They hope to define similar guidelines by which drugs can be designed and administered intranasally to treat neurological disorders.
“It would be interesting to use their approach to explore issues and opportunities for crossing the blood-brain barrier via intranasal administration,” DeSimone says.