'Large' nanoparticles find loophole in human mucus

By Susan Gotensparre

- Last updated on GMT

Related tags Immune system

US-based researchers have proven that 'large' nanoparticles can
pass through human mucus, which means that they could serve as
sustained-release carriers for drugs treating diseases affecting
the mucous membranes, such as cervical cancer.

Although large nanoparticles used to be considered immobile in the mucus, and so unsuitable for controlled drug delivery over periods longer than a few hours, the researchers at Johns's Hopkins University led by Dr Justin Hanes, got around this by coating them with low molecular weight polyethylene glycol (PEG) - a hydrophilic and uncharged polymer. They proved that large (200nm and 500nm) synthetic nanoparticles could penetrate human mucus to reach underlying cells rapidly, even faster than smaller nanoparticles (100nm), from which the release of drugs is hard to control.

Nanoparticles are of interest to drug developers because they minimise systemic toxicity and degradation of drug agent, and may reduce dosage frequency. In addition, 'large' nanoparticles provide sustained and localised drug delivery over days or even months and encapsulation is more efficient.

"It was shocking to see a synthetic particle moving so fast through mucus but this means we can deliver a lot of different drugs. The next step will be to use biodegradable particles,"​ Dr Justin Hanes told In-PharmaTechnologist.com.

The research team looked at viral properties to get a clue into how a synthetic particle could move through tissues. They took note of viruses being hydrophilic - water loving - and net neutrally charged and applied these properties to their nanoparticles.

"Viruses that can penetrate human mucus have a net neutral and hydrophilic surface that allows them to get through mucus without sticking to it. We wanted to mimic this. But we did not want use a genetically engineered protein, which could be recognised by the immune system like a virus. We wanted to find something that was neutral, hydrophilic and considered safe in pharmaceuticals - low molecular weight PEG ended up being ideal,"​ continued Hanes.

"Interestingly, PEG had previously been reported to be adhesive to mucus, but those studies used higher molecular weight versions of PEG that could stick to mucus in a Velcro-fashion."

The researchers compared PEG-coated particles with uncoated to see how rapidly they penetrate mucus in comparison to water. The research shows that large PEG-coated particles, 500nm and 200nm in diameter, diffused through mucus 4- and 6-fold more slowly than in water. The scientists also tested uncoated particles, 100-500nm in diameter, and the results showed that they diffused 2,400 - 40,000-fold more slowly in mucus in comparison to water.

Pharmaceutical firms have already shown interest over Hanes' technology, for which a few patents have been filed.

The researchers have described their results in a recent article in PNAS​ (online early edition, published the week of 22-26 January 2007).

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