Jan 24, 2007
Large nanoparticles pass though mucus
Polymer-coated nanoparticles as large as 500 nm across can rapidly diffuse into human mucus, according to new work by researchers in the US. The unexpected result could have important implications for treating diseases of the cervix, as well as for mucosal drug delivery in general.
Nanoparticles can be used to encapsulate drugs and deliver them to specific targets in the body so that they can treat diseases like those of the cervical tract, lungs, gastrointestinal tract and eyes. Larger particles are preferred because they can deliver drugs more slowly than smaller nanoparticles. Moreover, it is easier to encapsulate a wide array of drug molecules more efficiently in larger nanoparticles.
The human mucosal barrier, which can be up to several hundred microns thick, protects the body from foreign particles and flushes them out before they can cause damage to internal organs. Recent research has also shown that the mucus barrier blocks nanoparticles. Indeed, this research suggested that particles bigger than around 60 nm could not pass through the barrier, so limiting medical treatment options. Now, a research team led by Justin Hanes and Richard Cone at the John Hopkins University in Baltimore have shown that this is false and that nanoparticles as large as 500 nm can rapidly pass through mucus provided they are properly coated with a polymer first.
The researchers obtained their results by using a technique called high-speed multiple-particle tracking to observe the rates at which individual polymer-coated nanoparticles of various sizes diffused through samples of fresh cervical-vaginal mucus. This method analyses the trajectories of fluorescent particles using a special video camera. Cervical-vaginal mucus is very similar to the mucus found in many other human secretions – such as the airways of the lungs, gastrointestinal tract, nose and eyes – and the experiments were performed in a glass chamber under physiological conditions at 37 °C.
To their surprise, Hanes and co-workers found that, if coated with low molecular weight polyethylene glycol (a harmless mucus-resistant polymer routinely used in pharmaceutics), nanoparticles as big as 200 to 500 nm in diameter were able to rapidly move through the mucus. The particles had diffusion rates that were up to one-fourth as fast as those in pure water – a surprising result since the mucus used was about 2000 times more viscous than water. Another unexpected finding was that smaller polymer-coated particles of 100 nm in diameter moved 200 times slower than bigger particles – and not faster as commonly believed. In contrast, uncoated large particles moved up to 40 000 times slower than coated ones.
The results suggest that the so-called mucus mesh spacing, through which particles can pass, is much larger than previously thought: at least 500 nm as opposed to just 20 to 200 nm. The researchers believe that adding polyethylene glycol may prevent the nanoparticles adhering to the mucus so that they can pass through it more freely. Uncoated particles, on the other hand, quickly attach themselves to mucus and can cause it to clump together so that particles are blocked from entering further.
The results mean that large nanoparticles could be used for drug delivery through mucus in the future, say the researchers. Polymer-coated nanoparticles might also be extended to the delivery of drugs and antibodies that act at mucosal surfaces to block the entry of pathogens and so protect against viral infection and sexually transmitted diseases, the researchers added.
The work was published in the Proc. Natl. Acad. Sci..
About the author
Belle Dumé is acting editor of nanotechweb.org