24 April 2009 Sydney Morning Herald

Injections Now Seem Pointless

Needle-free Nanopatch Could Transform Vaccines

The end of painful needles is in sight. Patches will pierce the skin and deliver fewer toxins.

The end of deep, painful vaccine injections is in sight. One of the first widespread applications of nanotechnology in medicine could be a painless, needle-free vaccine "nanopatch" being developed by Australian scientists.

It also promises to bring much-needed protection against deadly diseases to people in remote areas where there is a lack of refrigeration or disposable syringes for traditional vaccines. A nanopatch could be sent by post.

an experimental microneedle array.

The size of an experimental microneedle array is shown by its placement on the researcher's finger.
There are 400 needles in the array. The nanopatch will have thousands.
Photo: Stanley Leary, courtesy of Georgia Tech Research

It will still pierce the skin. The centimetre-square silicon device has thousands of ultra-sharp microscopic spikes coated with dried vaccine. When applied lightly, it would cause no pain because it penetrates less than a hair's thickness below the surface.

This may not sound far, but it is another of the nanopatch's benefits, says Professor Peter Gray, the director of the Australian Institute for Bioengineering and Nanotechnology at the University of Queensland

The tiny spikes deliver vaccine close to where immune cells, known as dendritic cells, are found. Hypodermic injections, on the other hand, inject most of the vaccine too deep to activate these disease-fighters, making the vaccine less effective.

Many of our ancient microbial foes remain unconquered, says Gray. Polio has begun to break out again in Third World countries where it had been eradicated. Malaria is resurgent in tropical regions, measles still thrives, and an influenza pandemic is a constant threat.

"Eliminating or controlling diseases that have haunted humans for millennia requires a quantum leap in vaccine technology," Gray says.

Nanotechnology - the science of the very small - will provide some of these solutions, he says. Along with the nanopatch devised by Professor Mark Kendall, vaccines engineered to resemble viruses are also being developed at the institute, as well as nanoparticles that can deliver drugs to where they are needed in the body.

"Nanotechnology is medicine's next transforming technology," says Gray, who oversees 360 scientists and engineers.

The "nanospheres" being developed by Professor Michael Monteiro can deliver cancer drugs directly to tumours. Assembled out of multi-layers of carbon molecules called dendrimers that encapsulate the drug, the nanospheres are designed to have other molecules on their surface that can seek out and bind to cancer cells.

Cancer drugs are highly toxic, says Gray, and the trick is to deliver the drugs at doses that are high enough to kill the cancer without killing the patient: "Cancer therapy is an exercise in brinkmanship."

Nanosphere technology could make lower doses of drugs more efficient at destroying tumours by homing in on the cancer cells, and minimising damage to normal cells at the same time.

A simple and inexpensive way to make nanoparticles about 80 to 100 nanometres in diameter has also been developed by Professor Max Lu. These tiny mineral-like particles, made out of harmless substances used in antacid tablets, have a double-layered chemical structure that can surround and bind a drug, a piece of DNA or another snippet of genetic material which has the power to switch off genes or stop viruses replicating. Once the nanoparticle is inside a cell, it dissolves, releasing its medical package.

These nanoparticles will reduce the need for large doses of drugs, Gray predicts. They can be made into rod-like structures that can slip through the membrane into the nucleus of a cell. "This raises the possibility of using them as an alternative way of inserting genes into chromosomes to repair genetic defects," he says.

Our bodies are primed to detect and mount an attack against tiny viruses. Nanotechnologists have exploited this to make new vaccines that resemble viruses, so they trigger a powerful immune response. Professor Ian Frazer's cervical cancer vaccine, Gardasil, is an example.

These particles are about 50 nanometres across, and have a harmless core of a harmless virus protein, onto which are fused hundreds of copies of a protein from the virus targeted by the vaccine.

A promising vaccine against malaria was recently developed overseas using this nanotechnology, and Professor Anton Middelberg is working with other Australian researchers on a vaccine for rotavirus, which causes gastroenteritis and kills many children in poorer countries.

Mr Middelberg has developed a way to increase production of virus-like particles tenfold, by getting bacteria to make them. "This technique will allow manufacturers to rapidly modify vaccines to keep pace with fast-mutating viruses," Gray says.

That could come in handy in a pandemic when global demand for a vaccine would exceed production. Institute research suggests only 100th of the current dose would be needed if delivered on a nanopatch.

Source: Graeme O'Neill and Deborah Smith www.smh.com.au /...

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