|
 |
| Michel Lonji Kalombo |
Africa currently experiences the biggest tuberculosis (TB) epidemic in 60 years, with the occurrence of this disease in some countries having more than doubled between 1990 and 2005. Thus reads an article by two TB experts in the latest issue of The New England Journal of Medicine.
With only 11% of the world population, Africa accounts for more than a third of the world’s death rate due to TB. A Sunday newspaper ascribes a claim that the HIV pandemic is the greatest contributing factor to the growing TB death rate to Dr Richard Chaisson from the TB centre of the Johns Hopkins University. If TB is not timeously diagnosed and effectively treated, the infection spreads by air and people with inadequate immune systems are more vulnerable. In the recent outbreak of extreme drug-resistant TB (XDR-TB), more than 50% of HIV-positive patients in South Africa that contracted the disease, contracted it in hospitals and clinics. With several of these being health workers, the death rate for XDR-TB patients was higher than 95%.
At the forefront of the fight against the dreaded disease is CSIR senior researcher, Michel Lonji Kalombo. Hailing from the Democratic Republic of the Congo, Kalombo holds two engineering degrees (chemical and metallurgical) and is studying towards a PhD in applied science/chemical engineering at the University of Pretoria. His thesis is titled the ‘Design and development of anti-tuberculosis drugs-loaded nanocarriers’.
Kalombo also holds the rare honour as sole developer and inventor of the technology that enables the CSIR’s groundbreaking research on nanotechnology-based drug delivery. The system is capable of slowly releasing the drug in a controlled and sustained manner within human cells. This should help reduce dose frequency and thus patient compliance.
For effective treatment, patients suffering from the disease need to take anti-TB drugs (ATD) daily or several times a week for six to nine months. Patient non-compliance often results in treatment failure, as well as the emergence of MDR-TB. Treatment cost for MDR-TB is 100 times more expensive than normal TB, and about 50% of these patients die.
The CSIR research is undertaken in collaboration with various local and international institutions.The project aims to develop a nano-based drug-delivery system whereby anti-TB drugs can be administered in a reduced dose frequency, i.e. once every ten days for a shortened time period, as opposed to the current regimen of four antibiotics taken daily for six to nine months. The new delivery system should also ensure improved bio-availability and reduced toxicity. Once optimised, the research is positioned to have a remarkable impact not only in South Africa but also in the rest of Africa, since it holds promise for use in delivering anti-malaria drugs, anti-retrovirals for HIV/Aids patients, antibiotics, and many other drugs.
Kalombo designed and developed anti-TB drugs’ nanocapsules and optimised encapsulation efficiency, production yield, particle size and particle-size distribution, morphology and surface properties (e.g. zeta potential) of nanocapsules by monitoring various process parameters through different techniques including the multiple emulsion-evaporation technique, supercritical fluid, nano-precipitation, electrospinning and spray-drying.
He also assisted in in vitro drug-release and transport studies of nano-carriers across living tissues and membranes.
According to Kalombo, the dreaded TB is a real threat for humanity. “TB kills someone every 20 seconds - more than 2 million each year, according to the World Health Organization (WHO)”, he says. In addition, the deadly combination of HIV/Aids and TB complicates the management of the disease.
Being an airborne disease, the Mycobacterium tuberculosis (M. tuberculosis) causative agent of the pandemic easily gets entry into the body through airways. This explains why more than two billion people worldwide (one third of the population) are infected with TB at a dormant stage until external factors such as malnutrition, diabetes and HIV trigger its activity by compromising the immune system. This causes bacteria to enter and activate clinical symptoms of the disease. According to WHO, more than eight million people develop active TB annually. “HIV/Aids not only renders TB more lethal, it also complicates it by generating extra-pulmonary TB (affecting the brain, spine and bones), which is not easy to combat as these bacteria are located in ‘hide-aways’, almost unreachable and hampering its early detection when using conventional diagnostics.
The current daily four-drug TB regimen is efficient as long as the patient completes the course of the treatment over a period of at least six months.
“Unfortunately, in many cases TB patients do not comply with this lengthy and cumbersome treatment. The interruption of the treatment generally leads to the emergence of deadly TB strains that are resistant to the first-line regimen (MDR-TB) and ultimately even to the second-line drugs, resulting in XDR-TB, which is almost incurable,” he says.
Failures recorded in the treatment of various infectious diseases, such as TB, are associated with the poor systemic availability of the therapeutic compounds owing to their lack of absorption and also to the early clearance of the fraction that permeates through the epithelial cells by specific agents of the bio-defence system. These shortfalls induce the use of huge amounts of therapeutic agents, administrated for a very long period with an immediate consequence of patient non-compliance, leading ultimately to the development of very resistant strains of the infection.
The non-specificity of the current suite of drugs administered to patients affects the efficiency of the treatment, since it does not allow the drugs to reach therapeutic concentrations at the site-of-interest.
“We have been able to encapsulate the four frontline anti-tuberculosis drugs in nanoparticles made of biodegradable and biocompatible polymeric shells,” says Kalombo. Three inventions, with him as inventor, have been disclosed to make these nano-carriers ‘smart’ enough to be able to protect the drug during transit through the gastro-intestinal tract (GIT) and into circulation, as well as possible targeting to affected areas. This increases residence time at the site-of-interest while being able to escape macrophages as soon as they are in the systemic circulation.
“To tailor these to our requirements with regard to relevant physicochemical properties, such as size, size distribution, morphology, and surface charge, by using a single-step process readily scalable, has been a great achievement for our group,” beams Kalombo.
The research is currently at the preclinical phase where the product is being tested for determining pharmacokinetics and safety in mice.
|
