Tuberculosis, Nanomedicine & the Zebrafish: Bridging the gap between in vitro and in vivo models

Abstract

Tuberculosis (TB), caused by Mycobacterium tuberculosis, is a global health threat affecting millions of people and is one of the most deadly infectious diseases. The disease is curable, but current treatment regimens are lengthy and require daily dosing of several drugs that induces adverse effects, often resulting in patient non-compliance and treatment failure. The emergence of drug resistant M. tuberculosis strains is a major problem. Treatment of drug-resistant TB is limited and currently rely on less-effective and more toxic drugs. Therefore, we need new and more effective TB-drugs that could improve or replace current treatment options. In this thesis, I investigated the potential for enhanced TB treatment of current and experimental drugs by nanoparticle (NP) mediated delivery. The NP approach can improve the bioavailability of the drugs and enable sustained drug release and targeted delivery, resulting in increased efficacy and reduced toxicity. A selection of NPs and NP encapsulated TB-drugs where thoroughly investigated with respect to efficacy, toxicity and biodistribution using the zebrafish-TB model. Promising leads were identified and one nanoformulation progressed to testing in a mouse TB model. The screening systems and results presented can be valuable for the identification and ultimate approval of new TB-drugs