New active formulations against M. tuberculosis: Bedaquiline encapsulation in lipid nanoparticles and chitosan nanocapsules

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.Authors would like to acknowledge the public funding from Fondo Social de la DGA (grupos DGA), Ministerio de la Economía y Competitividad del Gobierno de España for the public founding of ProyectosI + D + i – ProgramaEstatal de Investigación, Desarrollo e InnovaciónOrientada a los Retos de la Sociedad (project n. SAF2014-54763-C2-2-R), the European Seventh Framework Program (NAREB Project 604237) and Ministerio de Educación Cultura y Deporte for SGE fellowship.Peer reviewe