The consortium of researchers, lead by the Council for Scientific and Industrial Research (CSIR), has successfully managed to encapsulate four first-line anti-TB drugs within a nano-sized polymeric shell, which could revolutionise the delivery of TB drugs and have a significant impact on the efficacy of therapeutic treatments in developing countries.
One of the major advantages of the new technique is that it would reduce the drug regimen for TB sufferers from four different drugs every day for up to six months, to a single treatment every seven days for just six weeks.
"The difficulty in treating TB results from patient non-compliance to the treatment regime," lead researcher on the project at CSIR, Dr Hulda Swai, explained to in-PharmaTechnologist.com.
"In a country such as South Africa…it is difficult to stick to the six-month-long treatment regime. In addition, once the patients take the treatment for a period of two months they feel better and stop taking the treatment."
It is patients quitting the treatment programme in this way that leads to the especially dangerous multidrug-resistant form of TB, which is resistant to at least isoniazid and rifampicin, the two most powerful anti-TB drugs. Over 400,000 new cases of multidrug-resistant TB are diagnosed every year.
Although drug resistant TB is essentially treatable through extensive chemotherapy (up to two years) and pricey second-line anti-TB drugs (which are also associated with severe adverse reactions), this isn't really a viable option for sufferers in sub-Saharan Africa, where TB is the number one killer.
"No new drugs [for TB] have entered the market in the last 50 years," says Swai, "thus while researchers are seeking other new drugs, we are looking into optimising the delivery systems for the current drugs."
And early findings show that their research has not been in vain. The team has successfully managed to encapsulate TB drugs isoniazid, rifampicin and pyrazinamide, with optimisation of ethambutol encapsulation currently underway.
The nanoparticles are submicron-sized polymeric colloidal particles within which the therapeutic agent is encapsulated, or adsorbed or conjugated into the surface. In in vitro tests, encapsulated drugs have been shown to be released in a slow, controlled fashion, and are protected from degradation in the intestines due to the polymeric shell.
The team has already demonstrated in vitro uptake of the encapsulated drugs in a human colorectal carcinoma line (CaCo-2), and is also working on a second cell line with the intention of assessing the system's suitability for pulmonary delivery.
As well as this, the research team is also working on a system for targeted delivery of encapsulated anti-TB drugs to infected cells within the lungs and other organs.
The collaborative effort, which brings together expertise from CSIR, the universities of South Africa, Pretoria, and Stellenbosch as well as Nottingham and Cardiff Universities, aims to develop biodegradable and biocompatible polymeric nano-carrier systems that will improve bio-availability of drugs and reduce dose frequency and treatment duration.
The new system would also have significant cost implications compared to current strategies, including the World Health Organization's (WHO) lauded DOTS programme (Directly Observed Treatment Short Course).
Under the DOTS framework, brought in to ensure patients stick to their medication and thus avoid cases of multidrug-resistant TB, patients swallow their tablets under the direct observation of a health worker every day for the first two months of treatment, and preferably for the entire duration of their six to eight month course of treatment.
According to Swai, the DOTS strategy simply doesn't work in sub-Sharan Africa, where the long distances patients have to travel to get to health clinics are costly and impractical.
"The [new] systems will be cheaper, particularly when taking into consideration the cost of the DOTS programme, which sometimes involves hospitalisation during the initial two months," said Swai.
"Also, shortening the treatment time will altogether reduce the direct and indirect cost of treatment."
All these features have an essential positive impact on patient compliance, and it is hoped will ultimately increase success rates in TB treatment and bring down the incidence of multidrug-resistant TB.
Once the drug delivery system has been perfected, the researchers believe it could have huge potential for use with other pharmaceuticals, for example in the treatment of malaria, HIV/AIDS and cancer.
"At present we are busy with animal studies and optimising the formulation, which should take about two years," said Swai.
"Once this phase has been completed, we will embark on clinical trials which will take another three years."
The WHO estimates that TB kills 5,000 people every single day, with the highest number of deaths and the highest mortality per capita occurring in the Africa region where 29 per cent of all TB cases occur.
Two billion people - one third of the global population - are infected with the bacilli that cause TB, 10 per cent of whom will develop active TB during their lifetime. HIV, particularly widespread in African regions, vastly increases the chances of contracting the disease, and has led to the increase in TB cases in the region hitting a staggering 20 per cent per year - much higher than the global annual figure of 3 per cent.
If Swai and colleagues' new drug delivery technique can curb this trend, the positive implications for TB sufferers in developing countries, let alone global public health, could prove it a significant therapeutic and economic contribution.
