Instituto de Nanociencia de Aragón, Universidad de Zaragoza and CIBER-BBN, Zaragoza, Spain, Univ. Grenoble Alpes, Grenoble, France, CEA, LETI, MINATEC Campus, Grenoble, France, Departamento de Microbiología (Facultad de Medicina), BIFI, Universidad de Zaragoza, Zaragoza, Spain, Instituto de Investigación Sanitaria Aragón (IIS-Aragón), Zaragoza, Spain, CIBER de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, Madrid, Spain, Instituto de Ciencias de Materiales de Aragón, Universidad de Zaragoza/CSIC and CIBER-BBN, Zaragoza, Spain, Nanoimmunotech, Vigo, Spain

In the last years, the increase in antimicrobial resistance, together with a lack of new drugs for the treatment of bacterial infections resistant to classical antibiotics are of growing concern. Moreover, some of current therapies induce severe side effects and are often difficult to administer. In 2012 the FDA approved the use of bedaquiline, as the first new very effective drug against TB in the last 40 years. Despite its effectiveness, unfortunately bedaquiline side effects can be so dangerous that at present it is to be prescribed only when no other treatment options are available. The development of effective and safe nanotechnology-based methods can be particularly relevant to increase antimicrobial concentration at the site of infection, to reduce doses in the general circulation, which in turn reduces adverse effects. In this work bedaquiline was encapsulated in two types of nanocarriers, lipid nanoparticles and chitosan-based nanocapsules with high encapsulation efficiency and drug loading values. The efficacy of the drug-encapsulating nanocarriers has been demonstrated in vitro against Mycobacterium tuberculosis, together with the excellent compatibility of both carriers with animal cells. The obtained results open the way for further studies on multi-drug resistant strains of M. tuberculosis and for in vivo studies of the optimized nanocarriers. The promising behaviour of drug-loaded nanocarriers will hopefully lead to a reduction of the administered doses of a quite dangerous drug as bedaquiline, tuning its biodistribution and so decreasing its adverse effects, finally allowing its use in a higher number of patients. © 2017 Elsevier B.V.

Bedaquiline, Cytotoxicicty, Electron microscopy, Mycobacterium tuberculosis, Nanocarriers

Chitin, Chitosan, Drug interactions, Electron microscopy, Encapsulation, Microorganisms, Nanocapsules, Nanoparticles, Antimicrobial resistances, Bacterial infections, Bedaquiline, Cytotoxicicty, Drug-resistant strains, Encapsulation efficiency, Mycobacterium tuberculosis, Nano-carriers, Drug dosage