Abstract
Tuberculosis (TB) is a disease caused by the bacterium Mycobacterium tuberculosis, a pathogen that has accompanied mankind throughout its far and recent history. Current TB-therapy consists of two treatment phases, one initial phase where a cocktail of four frontline anti-tubercular drugs are administered daily for a minimum of two months followed by a continuation phase where two or more drugs are taken for a minimum of four months. The extensiveness of the treatment is a problem as it becomes very costly and hampers patient lifestyle. In turn, this may lead to patient non-compliance and an increased probability of the emergence of drug resistant strains. There is thus a great need for developing new drugs and to improve the efficiency of current drugs. Our group has developed a method for encapsulating one of the frontline anti-TB drugs, rifampicin (RIF), in the biodegradable polymer Poly-Lactic-co-Glycolic-Acid (PLGA). The idea behind encapsulating the drug is to promote its gradual release, increase its residence time in the body, to promote a natural co-localization between drug and pathogen and by doing so, enhance the therapeutic effect of the drug. The main goal of my master project has been to develop and apply methods for measuring the effect of these PLGA-RIF-nanoparticles on zebrafish challenged with mycobacterial infection. The experiments reveal a decrease in bacterial burden accompanied by a significant increase in the survival of zebrafish larvae treated with these nanoparticles compared to their free-drug counterparts. This thesis therefore substantiates the claim that nanoparticle-based therapy holds real promise for the successful treatment of TB.