Researchers at the CSIR have developed a new nano-based drug delivery system that could bring TB patients in some of the poorest regions great benefits
An ambitious nano-drug delivery project for the treatment of infectious diseases, such as tuberculosis (TB), malaria and HIV/Aids is being led by Dr Hulda Swai, a senior researcher in polymers, ceramics and composites with CSIR Materials Science and Manufacturing. The project is a joint research initiative between the CSIR and a number of universities and research institutions, both locally and internationally. Dr Swai has headed up the initiative since 2002.
"The drawbacks of conventional treatment of infectious diseases calls for the development of a delivery or carrier system to release drugs slowly, over extended periods of time," she explains. "The new nano-drug delivery system addresses a number of key issues, such as patient non-compliance, toxicity, dose frequency, length of treatment, low bio-availability of drugs and is aimed at reducing the costs."
"In a developing/transitioning country like South Africa, the majority of people are poor and have to travel long distances to reach their nearest clinic or medical facility. As a result, it is very difficult to monitor patients and the DOTS program fails, and non-compliance becomes a huge challenge," Swai explains. "The new drug delivery system aims to shorten the duration of treatment, which will substantially improve patient compliance. The system will also ensure improved bioavailability." Diseases such as TB, malaria and HIV/Aids contribute significantly to the high mortality rate in Africa. Improved drug delivery will therefore impact on a range of socio-economic issues, including economic growth and poverty reduction. Once optimised, this delivery process has huge potential to be used in pharmaceuticals, not only in the case of TB, but also for the treatment of malaria and HIV/Aids.
Swai explains that the CSIR has managed to nano-encapsulate an anti-TB drug (isoniazid INH) in a biodegradable polymer with particle size ranging from 186 to 290 nm, through the double emulsion solvent evaporation method. This is the required size for oral or pulmonary nano-drug delivery. Says Swai, "We have also managed to alter the method slightly and have been able to make microparticles ranging from 700 nm to 500 µm (micrometres). The nanoparticles are submicron-sized (less than 1µm) polymeric colloidal particles with a therapeutic agent encapsulated within their polymeric matrix, or adsorbed or conjugated onto the surface. The release of the active agent may be constant over a long period; it may be cyclical; or it may be triggered by the environment or another external event." Her team has also performed cell studies, which indicated that the cells take up these polymeric nano particles. At this stage they are initiating animal studies with the MRC (Stellenbosch and Pretoria).
In addition, her group, in collaboration with an international University, EPFL in Switzerland has explored other polymeric systems with particles that are within 20-80 nm in size. Two anti-TB drugs, INH and Rifampicin, were encapsulated in these polymeric systems. Based on the in vitro drug release assays they performed it was demonstrated that the encapsulated drugs are released at a slower rate and for a prolonged period of up to 10 days, when compared with the free drugs. To take the mode of delivery to another level, her group is also working on targeted delivery of the drug with Nottingham University and Cardiff University (UK). This means the particles will be modified to allow targeting (localisation) of the particles to specific tissues or cells. The success of this approach will enable increased bioavailability, targeted delivery and thus reduce side effects.
Swai has been lauded for building up a large network of national and international partners to participate in the project. She has also been highly successful in securing funding for the initiative, and is in the process of submitting proposals in this regard to both the Wellcome Foundation, Swiss fund and the Gates Foundation.
Among many of Swai's objectives, training African Scientists in this vibrant field of nanotechnology is at the top of her list. She is currently mentoring five researchers working on the project. "Human capital development is one of our key focus areas, with researchers being trained at the University of London, the Swiss Institute of Technology (EPFL), the Nottingham School of Pharmacy, Pretoria University and the University of KwaZulu-Natal," she says.
Swai's interest in drug delivery was sparked while completing her PhD and working at the University of London in the late 1990s. "I was involved in the development of an anti-fungal slow-release device for HIV/Aids patients infected with Candida. This project made me aware of how useful polymer technology could be in addressing a number of key challenges in the treatment of infectious diseases," Swai recalls.
In line with her personal philosophy, Swai's future plans are not modest - she aims to establish an internationally-recognised multi-disciplinary research platform for drug delivery in all areas of treatment where non-compliance remains a challenge. Considering what she has already achieved, this goal seems well within her reach.