Novel Two-Phase Nanoparticles Readily Diffuse Through Mucus

The inner PSA core traps therapeutic agents inside the particles, while the particularly dense outer PEG coating allows the particles to move through mucus.

Results published in the November 9, 2009, online edition of the journal Proceedings of the [U.S.] National Academy of Sciences (PNAS) revealed that in fresh undiluted human cervicovaginal mucus (CVM), which has a bulk viscosity approximately 1,800-fold higher than water, PSA-PEG nanoparticles diffused at an average speed only 12-fold lower than the same particles in pure water. In contrast, similarly sized biodegradable nanoparticles composed of PSA or poly(lactic-co-glycolic acid) (PLGA) diffused at least 3,300-fold slower in CVM than in water. PSA-PEG particles also rapidly penetrated sputum expectorated from the lungs of patients with cystic fibrosis, a disease characterized by exceedingly dense mucus secretions. The rapid transport of the nanoparticles in mucus was made possible by the efficient partitioning of PEG to the particle surface during formulation.

PSA degrades into naturally occurring molecules that are broken down and flushed away by the body through the kidneys. As the particles break down, the drugs loaded inside are released.

"The major advance here is that we were able make biodegradable nanoparticles that can rapidly penetrate thick and sticky mucus secretions, and that these particles can transport a wide range of therapeutic molecules, from small molecules such as chemotherapeutics and steroids to macromolecules such as proteins and nucleic acids," said senior author Dr. Justin Hanes, professor of chemical and biomolecular engineering at Johns Hopkins University. "Previously, we could not get these kinds of sustained-release treatments through the body's sticky mucus layers effectively."

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