The
combination drug regimens that have long been used to treat
tuberculosis (TB), caused by Mycobacterium tuberculosis, are fraught with problems such as frequent administration, long
duration of treatment, and harsh adverse effects, leading to the emergence of multidrug resistance. Moreover, there is no effective preventive
vaccine against TB
infection. In this context, nanoparticles (NPs) have emerged as a potential alternative method for
drug delivery. Encapsulating
antibiotics in biodegradable NPs has been shown to provide effective
therapy and reduced toxicity against M.
tuberculosis in different mammalian models, when compared to conventional free
drug administration. Here, we evaluate the localization, therapeutic efficacy and toxic effects of polymeric micellar NPs encapsulating a promising but highly hydrophobic and toxic
antitubercular drug bedaquiline (BQ) in zebrafish embryos infected with Mycobacterium marinum. Our study shows that the NP formulation of BQ improves survival and reduces bacterial burden in the infected embryos
after treatment when compared to its free form. The intravenously injected BQ NPs have short circulation times due to their rapid and efficient uptake into the endothelial cells, as observed by correlative light and electron microscopy (CLEM).