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South Africa is using nanotechnology to improve existing tuberculosis drugs. Munyaradzi Makoni looks at a developing country's experience.

Treating tuberculosis (TB) in developing countries is a problem. Patients struggle to stick to the routine of taking daily tuberculosis medication for months on end — particularly when they must travel long distances for a nurse to ensure they take the drugs. This and the side effects mean many give up before completing the course.

Lack of adherence means the 50-year-old drug regimen is failing as multidrug-resistant strains emerge. Chances are remote that it will be replaced anytime soon with new antibiotics.

But the days of clockwatching for TB patients may soon be over. Researchers in South Africa are working on a way to deliver that half-century old treatment in a new guise — incorporating the drugs into nanoparticles so they are released slowly into a patient's bloodstream, raising the possibility that daily pills could be replaced with a single weekly dose.

Nanotechnology research is not cheap but researchers are hopeful that money spent on expensive research and development will be worthwhile when pitched against savings in treatment costs and substantial gains in health.

And those gains are there to be made. TB is one of the leading causes of adult death in South Africa with approximately 460,000 new TB cases in 2007, according to the WHO. South Africa is ranked fifth on the list of 22 high-burden TB countries in the world.

Old drugs repackaged

First-line treatment for TB consists of a pill of each of four antibiotics — isoniazid, rifampicin, pyrazinamide and ethambutol — taken every day.

South African scientists from the Council for Scientific and Industrial Research (CSIR) have incorporated these drugs into nanoparticles that are invisible to the human eye.

White blood cells take up nanoparticles because they look like foreign objects and, effectively, transport them throughout the body while releasing their cargo, says Hulda Swai, senior scientist at CSIR's Centre for Polymer Technology. "These nanoparticles have superior properties for absorption in the small intestine to improve bioavailability and uptake into the circulation," says Swai.

South African scientists from CSIR have incorporated traditional TB drugs into nanoparticles


The safety and uptake of the nanoparticles is being tested in TB-infected mice and the effectiveness of the nanodrug is being compared to conventional therapy to see whether a weekly nano dose is as effective as the standard daily treatment regime.

Human trials for the antibiotic, called Rifanano, are scheduled for 2012.

Affordability rules

But the trials are not spared problems that affect clinical trials in many developing countries.  

"Manpower and animal models are not always available, and where available, the expertise specific for nanomedicine is scarce," Swai told SciDev.Net.

But the potential advantages of the technology make its pursuit worthwhile. If TB treatment is reduced to a once-a-week dose, the overall costs, both of the drugs and of employing healthcare staff, could be significantly reduced.

"Given savings as a result of lower dose and higher efficacy, the consequence of targeted delivery — releasing drugs only after reaching the position required in the body treatments might actually become cheaper," says Bernard Fourie, chief scientific officer of Medicine in Need, a non-profit research organisation with a base in South Africa that aims to develop treatments and vaccines suited to the developing world.

Nanodrugs, tailored for delivery to the lungs or other sites of infected tissues have the potential to stop cancer cell growth, better protect against infection and more effectively attack and kill viruses and bacteria without affecting healthy cells around them.

"Remarkable benefits to healthcare" could be expected over the next decade with the development of drugs, vaccines and other pharmaceuticals that will specifically target diseased cells, Fourie says. But the major question, is whether such new technologies would also benefit poor populations, such as those in Sub-Saharan Africa where TB, HIV/AIDS and malaria continue to affect millions.

But Fourie believes South Africa's pharmaceutical industry is capable of adopting nanotechnology, and that availability and access to such nanomedicines shouldn't be a problem.

Swai agrees, saying: "Only a small fraction of treatment costs is actually related to the drug itself. The nanodrugs are designed to make use of cost-effective materials that are easily accessible and relatively cheap to manufacture."

Nanodrugs, tailored for specific delivery to the lungs means they can attack the virus without affecting healthy cells around them

Gary Hampton/ World Lung Foundation

And because the technology is home grown it will be less expensive to manufacture nanodrugs than to buy imported mainstream drugs, adds Swai.

Not just TB

CSIR researchers are also working on nanoencapsulating antiretrovirals and antimalarials, as well as second-line TB drugs used for resistant cases where the first-line drugs don't work.

For instance, nanoencapsulation can involve coating the anti-malaria drug chloroquine with nanomaterials that include liposomes which can deliver the drug by penetrating cell membranes, making their action on diseased cells more targeted and efficient.

CSIR is collaborating on this research with the African Institute for Biomedical Research in Zimbabwe, and the Kenya Medical Research Institute as well as institutes on other continents including the University of Brasilia and Federal University of Rio Grande du Sul in Brazil; India's Post Graduate Medical Research Institute and Life Care; and the University of Buenos Aires in Argentina.

Not without risk

Many researchers warn that the growing number of developing countries interested in nanomedicine need to be aware of the potential risks associated with nanotechnology.

Janice Limson, head of the Biotechnology Department at South Africa's Rhodes University, says: "The potential applications for nanomaterials are phenomenal, but researchers do agree that any developments in this regard must be partnered with research into understanding toxicity."

Materials have different properties at the nanoscale. For example, gold is nonreactive but at the nanoscale it becomes a catalyst for reactions.

While these properties are what make nanotechnologies so useful, they may also have unforeseen adverse effects. Globally, researchers are only just beginning to understand the toxicity of nanostructures and it is the subject of extensive work by a number of groups in South Africa.

First-line TB treatment consists of four antibiotics — isoniazid, rifampicin, pyrazinamide and ethambutol — taken every day

Andy Crump/ WHO/TDR

Andre Nel, chief scientist of the division of nanomedicine at the University of California in Los Angeles' NanoSystems Institute, says that there is a lot of interest in assessing whether the 'nanocarriers' that transport drugs have "hazardous effects that are different and independent from the drugs being delivered".

The former Stellenbosch University student says that so far the only studies on the effects of nanotechnology in animals have focused on industrial nanomaterials rather than those used in nanomedicine. He adds that the same screening methods will be used to look at the safety of nanodrugs.

Though unaware of any specific regulations to monitor the risk of nanodrugs in South Africa, Nel says most countries would like to have specific independent evaluation criteria for nanotherapeutics. But no set of risk factors specifically for nanotherapeutics has been indentified yet.

"Most agencies worldwide are basing their assessments on traditional methods of drug safety assessment in which the nanomaterial is regarded as an integral component of the therapeutic substance as there has been no special risk that evolved as a result of nanodrugs," he says.

But these hurdles do not prevent research teams in South Africa from forging ahead. The new TB drug delivery method has been slated for availability in government clinics in 2016.

And Swai and her team are already planning for the future. "We hope to undertake the nanoencapuslation of traditional actives - ingredients granted authorisation  used in treating other diseases of poverty around Africa such as sleeping sickness, ascariasis, leishmaniasis, chagas disease, onchocercariasis ," she says.

Munyaradzi Makoni is a freelance science journalist based in Cape Town, South Africa.

This article is part of a spotlight on Nanotechnology for health.