Johns Hopkins researchers say they have demonstrated, for the first time in animals, that nanoparticles can slip through mucus to deliver drugs directly to tissue surfaces in need of protection. The researchers used these mucus-penetrating particles (MPPs) to protect against vaginal herpes infections in mice and the goal is to create similar MPPs to deliver drugs that protect humans against sexually transmitted diseases or even treat cancer.
“This is the first in vivo proof that MPPs can improve distribution, retention, and protection by a drug applied to a mucosal surface,” said Justin Hanes, Ph.D., a professor of ophthalmology at the Johns Hopkins Wilmer Eye Institute, and director of the Center for Nanomedicine at the Johns Hopkins University School of Medicine. Hanes also is a principal investigator with the Johns Hopkins Center of Cancer Nanotechnology Excellence. Results of his experiments are described in the June 13, 2012, issue of the journal Science Translational Medicine.
The moist mucosal surfaces of the body, like the eyes, lungs, intestines, and genital tract, are protected from pathogens and toxins by layers of moist sticky mucus, which is constantly secreted and shed, forming our outermost protective barrier. “Although many people associate mucus with disgusting cold and cough symptoms, mucus is in fact a sticky barrier that helps keep you healthy” says Laura Ensign, a doctoral student affiliated with the Center for Nanomedicine at the School of Medicine and with the Department of Chemical and Biomolecular Engineering in the Whiting School of Engineering. She is the lead author of the journal report.
Unfortunately, Ensign noted, mucus barriers also stop helpful drug delivery, especially conventional nanoparticles intended for sustained drug delivery. In the Hopkins laboratory, researchers developed nanoparticles that do not stick to mucus so they can slip through to reach the cells on the mucosal surface, in this case the surface of the mouse vagina, she added.
Ensign explained that conventional nanoparticles actually stick to mucus before releasing their drug payload and are then removed when the mucus is replenished, often within minutes to hours. Working with researchers in the laboratory of Richard Cone, Ph.D., in the Department of Biophysics in the Krieger School of Arts and Sciences, the Hanes team fabricated particles with surface chemistry that mimics a key feature of viruses that readily infect mucosal surfaces.
“Richard Cone’s lab found that viruses, such as the human papilloma virus (HPV), could diffuse through human cervical mucus as fast as they diffuse through water. These ‘slippery viruses’ have surfaces that are ‘water-loving’ ” Hanes said. “In contrast, many nanoparticles intended to deliver drugs to mucosal surfaces are ‘mucoadhesive’ and ‘oil-loving’, but these nanoparticles stick to the superficial layers of the mucus barrier, the layers that are most rapidly removed.”
To make their mucus-penetrating particles, the team transformed conventional ‘oil-loving’ nanoparticles by coating them with a substance used in many commercial pharmaceutical products—polyethylene glycol (PEG). PEG makes the particles “water-loving,” like the viruses that slip right through mucus.
“The key is that the nanoparticles, like viruses, have to be small enough to go through the openings in the mucus mesh, and also have surfaces that mucus can’t stick to. If you think about it,” said Ensign, “mucus sticks to almost everything.”