Though no one diagnosed with cystic fibrosis has ever been cured, new research by Justin Hanes and his colleagues offers a potential solution to one of the biggest obstacles impeding treatment of this devastating and chronic illness—getting past the mucus barrier.
“The gene that could cure cystic fibrosis has been known since 1989. However, the disease hasn’t been cured because no one knows how to deliver the curative gene to cells lining the airways of the lungs,“ says Hanes, associate professor in the Department of Chemical and Biomolecular Engineering and an executive committee member of the Institute for NanoBioTechnology. “A major change in the next decade will be an increased focus on delivery technologies.“
Mucus, that sticky and highly viscous substance that lines the lungs, eyes, the gastrointestinal tract, and female reproductive tract is proficient at blocking particles from penetrating the body. This is a good thing when those particles are bacteria or viruses but bad when they are vehicles for life-saving therapies.
Hanes and fellow researchers are finding ways to get drug-delivering particles past those sticky mucus linings. Most importantly, they’re discovering how to get higher density nanoparticles through mucus at a faster pace, thereby beating the body’s speedy attempts to flush its contaminated mucus away.
In a paper published in the January 2007 Proceedings of the National Academy of Sciences, Hanes’ team reported that a coating of polyethylene glycol (PEG) keeps particles from sticking to mucus. PEG had previously been reported as highly adhesive to mucus, but the team showed that PEG molecules with low enough molecular weight (i.e., smaller versions of the molecule) were not.
In one of the most surprising and important findings, the researchers, including first author Samuel K. Lai (PhD candidate in Chemical and Biomolecular Engineering), demonstrated that particles coated with PEG moved through human mucus almost as fast as they move through water; particles without the coating had previously been shown to be completely immobile in human mucus.
The team also reported that openings in the mucus mesh lining are much larger than previously thought. This, in turn, means that much larger particles than once believed possible have the potential to pass through the protective mucus barrier, Hanes says. Larger particles are desired for commercial products since they are easier to efficiently load with drugs and are capable of sustaining the release of drug molecules for longer periods of time.
“These findings set the stage for a new generation of nanomedicines that can be delivered directly to affected areas to treat a host of important diseases, such as lung, colon, and cervical cancer, asthma, COPD (chronic obstructive pulmonary disease), inflammatory bowel disease, cystic fibrosis, and more,“ says Hanes.
The preceding article was adapted from “Bypassing the mucus barrier: a “Slick“ Answer“ by Angela Roberts in Johns Hopkins Engineering: The Magazine of the Johns Hopkins Whiting School of Engineering, Summer 2007.
To read the full text of this article: Lai, S.K., O’Hanlon, D.E., Harrold, S., Man, S.T., Wang Y., Cone, R., Hanes, J. (Jan. 23, 2007). Rapid transport of large polymeric nanoparticles in fresh undiluted human mucus. Proceedings of the National Academy of Sciences 104, 1482-1487, please click here.
Read more: Coated Nanoparticles Solve Sticky Drug-Delivery Problem on Headlines at Hopkins