Professor Viness Pillay, professor of pharmaceutics and NRF research chair in the Department of Pharmacy and Pharmacology, at Wits University, says working at the nanoscale allows researchers to harness new properties of particles, as they behave differently at an atomic level.
Nanoparticles have dimensions in nanometres (nm), or one billionth of a metre. To get an idea of the size, picture a human hair – that's a hefty 80 000nm. While nanoparticles are generally defined as structures with dimensions of less than 100nm, for biomedical purposes, it's often necessary to go much smaller.
For the kind of drug delivery systems Pillay is involved in, for example, researchers need to go down to around to 25nm, so they can start playing at the cellular level. At this size, he explains, nanoparticles can play a role in intra-cell drug delivery. “We don't just want the drug to circulate in the bloodstream; we want it to get inside the cell.”
According to Pillay, there are many disorders, including motor neuron diseases, where a genetic alteration has occurred inside the cell, which needs repairing in order to treat it. “Many current treatments for neurodegenerative diseases merely prolong the patient's life, without being able to cure the disorder,” explains Pillay. “Nanotechnology enables drugs to work on the mitochondria inside cells, which might have undergone a genetic alteration.”Pillay serves as director of the Wits Drug Delivery Platform (WDDP), where a team of over 50 researchers is working on several technologies that have potential for commercialisation. His research essentially involves working on nanostructures to be able to target specific areas in the body, to create efficient drug delivery systems.
“Nanostructures are composed of a host of archetypes – nanoparticles, nanotubes, nanosensors; so you focus on choosing an archetype and design depending on which area of the body you want the drug to target.”
Another application, which sounds grimmer than it is, is an intra-ocular implant. “The 'Bio-response intelligent intracellular ocular implant', or BI3, works in response to inflammation,” explains Pillay. It's for posterior segment disorders, where inflammation occurs deep within the eye, which eye-drops can't get to. The biodegradable system, about 5mm in diameter, is implanted in the back of the eye and releases both an antibiotic and anti-inflammatory.
“The nano-enabled system is intelligent and bio-responsive because it reacts only in the presence of inflammation,” notes Pillay. He explains that inflammation releases free radicals, which react with the polymer system, which degrades to release the drug. “The implants are tailor-made for the patient, depending on the severity and period of the inflammation. In some cases, such as patients in advanced stages of HIV, if you don't treat posterior eye disorder they can go blind.”
While most of the technology is still in the preclinical phase, Pillay says some projects will soon undergo “first-in-man” studies, and they plan to test the technology further. This will hopefully be enabled by funding from the Department of Science and Technology and the Technology Innovation Agency, which has invested more than R25 million in the Wits platform.
Dr Thavi Govender, from the University of KwaZulu-Natal's School of Pharmacy and Pharmacology, is investigating the use of nanoparticles to create both an artificial enzyme and a chaperone molecule to help prevent proteins from accumulating around cells. This could be used to treat diseases such as Alzheimer's and type two diabetes, which fall under a class of disorders where amyloid protein build-up takes place.
Govender says the aim is to combine the work of two research groups to create a new method for evaluating potential type two diabetes drugs. “Type two diabetes is the biggest killer in the world, and the main problem is there's no tool for pharmaceutical industries to determine how well another molecule will bind the protein,” says Govender. “They usually have a bank of 10 000 or 20 000 molecules, which they can screen until they get a hit, but there's no tool for them to use for these diseases,” he explains.
The UKZN team, working in collaboration with researchers from pharmaceutical company Astrazeneca, hopes to derive a rapid methodology for analysing new drug efficiencies. “We wish to develop a method whereby novel potential type two diabetes inhibitors can be rapidly tested. Govender says the first step is synthesising modified amylin proteins.
“People have always dreamed of making an artificial enzyme, as it could lead to the ultimate cure for any disease. With nanoparticles, it could be possible to make a structure that behaves like an enzyme. It's a dream at the moment, but we believe it can be done.”
Another aim, notes Govender, is to investigate the use of nanoparticles to act as an inhibitor for these disorders. They're exploring the possibility of applying specially designed nanostructures that are membrane-bound, to prevent the accumulation of peptides into insoluble plaques. This may lead to a new approach in anti-diabetic therapeutics, he adds.
Govender explains that the diabetes-associated peptide is secreted by pancreatic beta-cells, together with insulin. This protein can cause damage when it aggregates outside the cells and comes into close contact with cell membranes. His team is trying to create a chaperone protein, which carries certain molecules from place to place in the body. ”Using nanoparticles, which are taken up quickly by cells, to bind the protein, means it will be absorbed into the cell where it can be destroyed.”
While several drugs are available for non-insulin-dependent diabetes, Govender points out that these agents simply maintain insulin at 'normal' levels, rather than preventing the progression of the disease. “We have already identified which molecules can treat the problem, and we're now in the process of determining how to deliver molecules to the right parts of the body.”
The main aim, says Govender, is taking these innovations from the lab to real life. “As scientists, we never do something just for the sake of it; we're trying to make a difference.”
While it's one thing working on cutting-edge solutions in a lab environment, it's quite another bringing them to market. Pillay says for every product being developed as part of the WDDP, they apply for patents in SA, and also in the US, UK, and Japan, where the major pharmaceutical players are situated.
According to Pillay, their research work incorporates two approaches – a scientific model and a business model. “We work in close conjunction with our technology transfer office, Wits Enterprise, which is involved in the commercialisation of the technology down the road.
“What we want is for these technologies to become available to patients to use. We don't just want to create a whole lot of patents to sit on a shelf or publications in journals – it must be available for use.”
He adds, however, that this is not an easy process. ”It involves discussions with large multi-nationals, venture capital companies, angel funders, and so on. We really want to showcase the technology so people can see its advantages and investors can get involved.
“We're prepared to show government the superiority of the technology, and hopefully get them to fast-track the technology and get it to market, without compromising the scientific process.”
He notes that, while funding for nanotechnology is being made available, nanoscience is a very expensive field. “The equipment, especially imaging tools, is very costly – we have recently been awarded an imaging system for R8 million.”
Govender adds that government prioritises HIV, TB and malaria-related research, as these are major concerns for SA and Africa. “Our country is doing the right thing by focusing on what the problems are in SA.”
While theses advances herald significant breakthroughs in preventing and treating disease, there are still many unknowns regarding the long-term effects of using nanoparticles inside the body.
“Internationally, scientists are running into highly restrictive regulatory barriers,” explains Pillay. “You can come up with a fantastic product, but get nowhere because the regulations around nanotechnology are very hazy.”
He explains that, from a scientific viewpoint, the concern is understandable. “If you take molecules from their normal state to the nanostate, you change their chemistry completely, and if you aren't careful enough, it could create toxicity in cells, genetic mutations – there's a huge debate going on around toxicity.”
Govender adds that scientists have to consider the implications if nanoparticles are sitting all across the body, or stored in various organs. “We don't really understand what happens, but we're exploring the positive aspects of the technology, and seeing what it can do, and then we'll work around the potential negative aspects.”
“There are challenges, but you shouldn't stop scientific progress because of challenges, says Pillay. “It should spur you on to prove which are non-feasible technologies, and which can be fantastically enabling.”
In future, predicts Pillay, nanotechnology's role in healthcare could bring about effective disease prevention systems. “I foresee people looking at bio-robotic-type systems, where a nanochip will potentially be able to detect diseases before they manifest by monitoring the body's biochemical and genetic make-up.
“For example, one of our projects involves nanosensors that could detect changes in the biochemical climate and feed it back into the biological system.” Through this feedback loop, explains Pillay, you can change things in the system before they develop into potentially life-threatening illnesses.
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