Delivery of efficient anti-Tuberculosis drugs

Tuberculosis (TB), a serious human disease, is caused by a bacterium known as Mycobacterium tuberculosis (Mtb). TB can be deadly and accounts for higher mortality specially in developing country, mainly due to malnutrition, low immunity and HIV coinfection. Treatment of TB with first line anti-TB drugs/antibiotics lasts for six months, while drug-resistant TB requires the implementation of second-line drugs which lasts over two years. Due to toxicity of anti-TB drugs, there is poor treatment compliance, which results in disease relapse and emergence of drug resistant Mtb.

This Medical and Life Sciences Research Fund project led by Dr Pooja Agarwal aims to employ nanocarrier based drug delivery of anti-TB drugs in macrophages. For cell specific delivery, the Warwick Medical School and Coventry Hospital team have developed nanoparticles with mannose residues attached to their surface which bind to the mannose receptors present on macrophages.

For this study anti-TB drug rifampicin has been encapsulated in the core of these nanoparticles. This encapsulated drug will be used to target laboratory and clinical strains of Mtb inside macrophages, and the activity will be compared with free rifampicin. Also propose is a novel treatment strategy to reduce the mycobacterial load in murine model by delivering encapsulated drug in combination with free rifampicin.